Pharmacology Flashcards
What is pharmacology?
The study of the effect of drugs
Define druggability
Used in drug discovery to describe a biological target that is predicted to bind with high affinity to a drug.
What are the 4 types of drug targets?
- Receptors
- Enzymes
- Transporters
- Ion channels
Define receptor.
A component of a cell that interacts with a specific ligand (exogenous or endogenous) and initiates a change of biochemical events leading to the ligands observed effects.
(ligand receptor only present on certain cells)
What are 3 types of chemical signals that use receptors?
- Neurotransmitters
e.g., acetylcholine, serotonin - Autacoids
e.g. cytokine , histamine - Hormones
e.g. testosterone, hydrocortisone
What are 4 types of receptors?
- Ligand-gated ion channels
e.g. nicotinic ACh receptor - G protein coupled receptors
e.g. beta-adrenoceptors - Kinase-linked receptors
e.g. receptors for growth factors - Cytosolic/nuclear receptors
e.g. steroid receptors
Explain what ligand gated ion channels are?
Are pore forming membrane proteins that allow ions to pass through the channel pore so that the cell undergoes a shift in electric charge
- change in charge can be mediated by an influx of cation or efflux of anion
What receptors do ligand-gated ion channels have?
Nicotinic ACh receptors
Explain how G protein coupled receptors work.
Guanine Nucleotide-binding proteins
- Largest group of membrane receptors
- needs to interact with a G protein
- guanosine triphosphate (GTP) and guanosine diphosphate (GDP) binding are controlled
- G proteins act as switches
Explain the function of Kinase-linked receptors.
Kinases catalyse the transfer of phosphate groups between proteins - phosphorylation
- substrate gains a phosphate group ‘donated’ by ATP
- causes conformational change
What receptors do G protein coupled receptors have?
- M3R (muscarinic receptor)
- Beta-2-adrenorecepto. Produces second messenger cyclic-AMP
What are kinase-linked receptors targets for?
Growth factors
Explain the function of nuclear/cytosolic receptors.
Work by modifying gene transcription
(steroid hormones - require ligand binding site)
What are cytosolic receptors targets for?
Steroids
Define agonist
A compound that binds to a receptor and activates it
Define antagonist.
A compound that reduces the effect of an agonist.
Define the two state model of receptor activation.
Drugs activate receptors by inducing or supporting a conformational change in the receptor from ‘off’ to ‘on’
Define efficacy
How well a ligand activates a receptor
How well it induces a conformational change
Define potency
The amount of drug needed to produce a given effect.
What is the difference between a competitive and non-competitive antagonist?
Competitive = binds to the same site
Non = Binds to an allosteric site on the receptor to prevent activation of receptor
What is EC50 and what does it tell us about a drug?
EC50 = the conc of drug that give half the maximal response
Its potency!
What does Emax tell us about a drug?
Efficacy - The maximum response achievable
What is intrinsic activity?
- Emax of partial agonist/Emax of full agonist
- Basically, how well a drug works against something that fully works
Does an antagonist show efficacy?
No.
An antagonist has affinity but zero efficacy.
An agonist however demonstrates affinity and efficacy.
Which is more efficacious, a full agonist or partial agonist?
A full agonist is more efficacious because a full agonist can give a 100% response.
Define affinity.
How well a ligand binds to the receptor.
What 2 main factors govern drug action?
- Receptor-related
- affinity
- efficacy - Tissue related
- receptor number
- signal amplification
What is the effect of fewer receptors on drug potency?
Fewer receptors will shift the dose-response curve to the RHS, this means drug potency will be reduced.
What is the effect of fewer receptors on receptor response?
Receptor response is still 100% due to receptor reserve. (Partial agonists don’t have receptor reserve).
What is the affect of less signal amplification on drug response?
Less signal amplification gives a reduced drug response.
Describe allosteric modulation.
An allosteric modulator binds to a different site on a receptor and influences the role of an agonist.
What is inverse agonism?
Where an agonist has a negative effect at a receptor.
Pharmacology: define tolerance.
A reduction in the effect of a drug overtime. This can be due to continuous use of repeatedly high concentrations.
Why is selectivity used to describe drug targeting rather than specificity?
Because no compound is truly specific
Give an example of a drug that is highly selective and one that is not?
- Isoprenaline is a non-selective B-adrenoreceptor agonist it activates both heart (B1) and lung (B2) receptors
- Salbutamol is a selective B”-adrenoreceptor and only activates lung (B2) receptors
What 3 ways can a receptor be desensitised?
- Uncoupled (an agonist would be unable to interact with a GPCR).
- Internalised (endocytosis, the receptor is taken into vesicles in the cell).
- Degraded. (no longer functions properly)
What is signal transduction and amplification?
Transduction = process involving conversion of a signal from outside the cell to a functional change within the cell
Amplification = to increase the strength of a signal
What are the 2 types of enzyme inhibitors?
- Irreversible inhibitors
- react with the enzyme and change it chemically
- covalent bond - Reversible
- bind non-covalently and induce different inhibitions depending on location of bond
Explain how statins work?
- Block the rate limiting step in cholesterol pathway
- reduces level of ‘bad cholesterol’
- reduce cardiovascular disease
How do ACE inhibitors work?
- Angiotensinogen (liver) is converted to angiotensin 1 via renin (kidney).
- Angiotensin 1 is then converted to angiotensin 2 via ACE (lungs).
- ACE inhibitors prevents angiotensin 1 binding and so you don’t get angiotensin 2 formation.
(Angiotensin 2 is a vasoconstrictor and so ACE can be used in the treatment of hypertension).
Name a drug that targets enzymes?
NSAIDs
What is the action of NSAIDs?
- They inhibit the COX enzyme (competitive inhibitors)
- COX is responsible for the breakdown of arachidonic acid to prostaglandin H2 (PGH2)
- reduce prostaglandin production = can lead to stomach ulcers
How is Aspirin different to other NSAIDs?
It irreversibly blocks the active site of COX resulting in irreversible inactivation
Give an example of a disease where the enzymes target multiple step in the pathway.
Parkinson’s Disease
Define synergy
Interactions of drugs such that the total effect is greater than the sum of individual effects
e.g. paracetamol & morphine/ibuprofen
(1+1>2)
Define pharmodynamics.
the effect of the drug on the body
Define pharmacokinetics
What the body does with the drug
What is an example of a physiochemical reaction?
the adsorption of paracetamol by activated charcoal as a treatment of paracetamol overdose
Define summation.
Different drugs used together to increase the effect of a single drug
(1+1=2)
How can some drug interactions be antagonistic?
When 2 drugs are given but they act against each other and blocks the action
(1+1=0)
Define potentiation.
enhancement of one drug by another so that one drug becomes more potent but the other one stays the same
(1+1=1+1.5)
What is the mechanism of pharmacokinetics?
AD ME
Absorption
Distribution
Metabolism
Excretion
Define bioavailability
The fraction of an administered drug that reaches the systemic circulation.
e.g. IV is always 100% but orally less
What are the factors affecting absorption?
- Motility - if the gut has slowed digestion, the drugs won’t work as well. A drug interaction that affects speed of absorption
- Acidity - all drugs are either ionised or unionised, can affect whether a drug passes through membrane
Explain drug distribution
Drugs can go into the proteins, other tissues or the effected site
How does protein binding affect strength of drugs?
If you give 2 highly protein bound drugs, they will make each other stronger and increase their effect
- the drug bound to the protein has no effect, but the drug bound to that drug is then free to have an effect
(make sure you check what other drugs a patient is on)
How does drug inhibition effect drug metabolism?
inhibition = Drug A blocks metabolism of Drug B, leaving more free drug B in the plasma so it has an increased effect
How do drug interactions effect excretion?
Weak bases - cleared faster if urine acidic
Weak acids - cleared faster if urine alkali
What drugs cause acute kidney injury?
NSAIDs
ACEi
Gentimicin
Furosemide
How does enzyme induction effect drug metabolism?
Induction
- Drug C induced CYP450 isoenzyme leading to increased metabolism of Drug D so it has decreased effect
- drugs can cause an increase in liver enzyme activity
- broken down into metabolite quickly so now have decreased efficacy (unless metabolite is active)
Examples of diseases that are due to imbalance of chemicals/receptors
Chemicals
- Allergy; increased histamine
- Parkinson’s; reduced dopamine
Receptors
- Myasthenia gravis; loss of Ach receptors
- Mastocytosis; increased c-kit receptors
Define selectivity.
The degree to which a drug acts on a given site relative to other sites
Define specificity.
The measure of a receptors ability to respond to a single ligand.
Give 2 types of cholinergic receptors?
- Muscarinic
- Nicotinic
What are the 2 types of ion transport?
- Passive
- symporter (transport in 2 in same direction)
- channels - Active
- ATP-ases
What are uniporters?
Use energy from ATP to pull molecules in
What are symporters?
Use the movement of one molecule to pull in another molecule against a concentration gradient
(transport 2 molecules at same time in same direction)
What are antiporters?
One substance moves against its gradient, using energy from the second substance moving down its gradient
Example of symporter
Na-K-Cl cotransporter is a protein that transports Na, K and Cl into cells
- all move in same direction
Explain epithelial sodium channels?
- selectively permeable to Na+ ions
- causes reabsorption at collecting ducts
- blocked by amiloirde
- used as anti-hypertensive
Explain voltage gated calcium channels
- Found in membrane of excitable cells
- at resting membrane potential closed
- activated by depolarised membrane potential
- Ca2+ enters the cell
What drug inhibits voltage gated calcium channels?
Amlodipine (calcium channel blocker)
- inhibits movement of Ca ions
- inhibiting contraction of muscles
-lowering blood pressure
Define xenobiotics
Compunds that are foreign to an organism’s normal biochemistry, such as a drug or poison
What is the role of cytochrome P450?
- Metabolise drugs
- deactivate molecules so they can be excreted
Define afferent
Carries signals towards the brain or spinal cord
Define efferent
Carries signals away from the brain or spinal cord
Define adrenergic.
Relating to adrenaline or noradrenaline and their receptors.
Define cholinergic
Relating to acetylcholine and its receptors.
Define autonomic
Acting or occurring involuntarily
- then divide into parasympathetic and sympathetic
What are muscarinic and nicotinic?
Types of ACh receptors
Define ganglion
A group of nerves
What are the differences between somatic and autonomic NS?
Somatic:
- single neurone between CNS and skeletal muscle
- innervates skeletal muscle
- leads to muscle excitation
Autonomic:
- 2 neurone chain
- cranial nerve 3,7,9,10
- smooth muscle, cardiac muscle, glands
- leads to excitation or inhibition
Is the postganglionic neuron closer to the effector organ in the sympathetic or parasympathetic nervous system
Parasympathetic
Explain the different nervous system fibres?
Somatic = one long fibre
Parasympathetic = 2 neurones, with ganglion within a chain adjacent to spinal cord
Sympathetic = 2 neurones with ganglion within or very close to effector organ
What receptors are involved in parasympathetic nervous system?
Preganglionic = ACh (N2 receptor)
Post-ganglionic = Ach (Muscarinic receptor)
What receptors are involved in sympathetic nervous system?
Preganglionic = ACh (N2 receptor)
Post-ganglionic = Noradrenaline (alpha and beta receptors)
What does nicotine do?
Stimulates sympathetic and parasympathetic nervous system
What does muscarine do?
Activates muscatinic receptors of the parasympathetic nervous system
What are the 5 types of muscarinic receptors?
M1: Brain
M2: Heart (SA node)
M3: All organs with parasympathetic innervation
M4: Mainly CNS
M5: Mainly CNS
Where are muscarinic receptors located?
Outside the cell and activate intracellular processes through G-proteins
What affect do M2 receptors have on the body?
Activation on SA node
- decreases heart rate
Activation on AV node
- decrease conduction velocity
- induces AV node block (increase PR interval)
What do M3 receptors do when stimulated in the respiratory system?
Stimulation in the respiratory system
- produces mucus
- induces smooth muscle contraction
What do M3 receptors do when stimulated in the skin?
- Only place where sympathetic system releases ACh
- Stimulation causes sweating
What do M3 receptors do when stimulated in the GI tract?
GI tract
- increase saliva production
- increase gut motility
- stimulates biliary secretion
What do M3 receptors do when stimulated in the urinary system?
- Contracts detrusor muscle
- Relaxation of internal urethral sphincter
What do M3 receptors do when stimulated in the eye?
- Causes myosis (pupil constriction)
- Increases drainage of aqueous humour
- Secretion of tears
What do muscarinic agonists do to the eyes?
- increases drainage of aqueous humour
- reduces ocular pressure
- treats acute glaucoma (disease that damages optic nerve and reduces vision)
- treat dry mouth
Use of muscarinic antagonists
- increase heart rate
- treat bradyarrythmias
- AV node block
- reduce salivations
- reduce bowel obstruction
What are some functions of anti-muscarinics?
- Bronchodilation
- Dry mouth
- urinary retention
- slows gut contractibility -> treatment for irritable bowel syndrome
Give some uses of ACh outside the ANS?
- botulinum toxin (botox) prevents ACh release
- cause flaccid paralysis and death
- treat painful muscle spasms
How is acetylcholine inhibited?
Nicotinic (N1) receptor blockers inhibit ACh activity in the somatic nervous system
Explain myasthenia gravis disease?
- blockage of acetylcholine receptors
- body makes antibodies that bind to these receptors
–> repeated movements become difficult & tiring
Name some Nicotinic antagonists and how they work
- Curare, Pancuronium (relax skeletal muscles during surgery)
- Compete with ACh for binding to the nicotinic receptor
Where are noradrenaline and adrenaline released from?
Adrenaline = adrenal medulla
Noradrenaline = adrenal medulla + sympathetic nerve fibre ends
What is the pathway from L.dopa to adrenaline?
It is the precursor to them
L-dopa –> dopamine –> noradrenaline –> adrenaline
How many alpha and beta receptors are there?
Alpha 1 & 2
Beta 1, 2 & 3
What is the function of alpha 1 receptors agonists?
Contracts smooth muscle
(pro-sympathetic)
- vasoconstriction (in skin and abdominal beds)
-> more blood can go to heart etc. - increase in peripheral resistance
- increased blood pressure
- increased closure of internal sphincter of the bladder
(greater affinity to bind to noradrenaline)
When would Alpha 1 agonists be used?
- Noradrenaline is given IV for shock
- Also used to overcome anaesthetic agents
- Adrenaline can be used to overcome anaphylaxis
- Xylometazoline can be used as a nasal decongestion
What is the function of alpha 2 agonists?
Mixed effects on smooth muscle
(anti-sympathetic)
- exist in brain
- increase concentration
- reduces vascular tone
- reduces blood pressure
- inhibition of noradrenaline, ACh and insulin release
(same binding affinity to adrenaline and noradrenaline)
Name an Alpha 2 agonist.
- Clonidine can be used in ADHD to help concentration
How are alpha 1 antagonists used?
- lower blood pressure
- block tamsulosin in benign prostatic hypertrophy
How are alpha 2 antagonists used?
- antidepressant
Not used clinically.
What is the use of beta 1 receptors?
Mainly in: heart, kidney, fat cells
- tachycardia (positive chronotropic)
- increase in stroke volume (positively ionotropic)
- increase renin release
- increase lipolysis and hyperglycaemia
(Same binding affinity to adrenaline and noradrenaline)
What is the function of beta 1 blockers?
- Reduce heart rate
- Reduce stroke volume
- Reduce myocardial oxygen demand and help remodelling in heart failure or post-myocardial infarction
E.g. carvedilol, bisoprolol, atenolol… - bronchoconstriction (careful in asthma)
What is the effect of beta 2 receptors on different tissues?
Vasodilation
Bronchi = bronchodilation
Bladder wall = inhibits micturition
Uterus = Inhibition of labour, relaxation of uterine muscles
Skeletal muscle = increase contraction speed
Pancreas = increase insulin and glucagon secretion
(greater binding affinity to adrenaline than noradrenaline)
When is a beta 2 agonist useful?
- Asthma/COPD (side effect hyperglycemia and tachyarrhythmia)
- Can be used to delay labour
Salbutamol is an example
What are the characteristics of GABA receptors?
- many different drugs binds to different places on the receptor
- used in anxiety
- in CNS
e.g. Benzadiazepenes, ethanol, barbiturates
What are the different histamine receptors?
H1 = allergies, IgE
H2 = Gastric acid secretion, GORD
What are routes of administration of opioids?
Pharmacokinetics
- oral -> bioavailability (first pass metabolism by the liver so only take in 50%)
Parenteral (given anywhere else in the body than the mouth)
- subcutaneous (Intravenous or Intramuscular)
- IV PCA (patient controlled analgesia - fall asleep before given too much)
- Epidural/CSF
- Transdermal patches
How do opioids work?
Use the existing pain modulation system
- descending inhibition of pain (stops fight or flight)
- use G protein coupled receptors (act via second messengers)
- inhibit release of pain transmitters at spinal cord and midbrain (release endorphins instead)
- change pain perception in higher centre
- change emotional perception of pain
Give some examples of opioid receptors
MOP (morphine - this is the one we actually use in drugs)
KOP (kappa receptors)
DOP (delta receptors)
NOP (nociceptin opioid-like receptors)
What is the main opioid receptor, that all the drugs we currently use act on?
μ (Kappa) receptors
(MOP)
Define tolerance
Down regulation of the receptors with prolonged use. Need higher doses to achieve the same effect.
Define dependance: symptoms showing dependance.
Psychological = craving, euphoria
Physical effects
Define the length of an opioid withdrawal?
Starts within 24 hours, lasts about 72 hours
What are the side effects of opioids?
- Respiratory depression
- sedation
- nausea + vomiting
- constipation
- itching
- immune suppression
- endocrine effects
What are the risks of taking opioids?
ADDICTION
- slowly reduce dosage to reduce withdrawal effects
Explain the metabolism of morphine?
Morphine –> morphine 6 glucuronide (more potent & usually excreted quickly)
- in renal failure it will build up and cause respiratory depression
What is respiratory depression?
Slow and ineffective breathing
- lungs fail to exchange carbon dioxide and oxygen
What are opioids?
Any drug the binds to opioid receptors in the brain
- derived from the morphine poppy
What are the 4 types of opioids?
- Naturally occurring - opium poppy e.g. morphine, codeine
- Simple chemical modifications e.g. diamorphine (heroin)
- Synthetic opioids e.g. pethidine
- Synthetic partial agonists (weaker) e.g. buprenorphine
How do people respond to opioids differently due to pharmogenetics?
- 10% of people have a gene that makes opioids ineffective to them
- 5% of people have gene that overreacts to opioids
What is the antidote for morphine?
Anatgonist = Naloxone
What does opium contain?
Morphine and codeine
Where do opioid receptors exist?
In the brain - where we want to target
Also in:
- digestive tract
- respiratory control reserve
- spine
(this is why side effects occur)
Define drug development
The process of bringing a new pharmaceutical drug to the market.
Where are drugs developed from?
- Plants
- Inorganic elements
- Organic molecules
- Sulphonamide Nucleus
- Bacteria/fungi/moulds
- Stereoisomers
- Immunotherapy - antibody based vaccines, monoclonal antibodies
- Recombinant proteins/steroids - insulin
- Animals - insulin, steroids
- Drugs targeting DNA
- Gene therapy
- High throughput assays/rational design
What are the pharmacokinetic issues for immunotherapy?
- Immunoglobulin - not filtered by kidney
- FcRn receptor - systemic receptors which absorb IgG into cells protecting them from metabolism
- Mouse antibodies - shorter half life
What receptors do steroids use to work?
Work through nuclear hormone receptors
What is a gene therapy?
Replacing a mutated gene that causes disease with a healthy copy of the gene
- inactivate or ‘knocking out’ mutated gene
- introduce new gene to help fight disease
Define rational drug design.
The process of finding new medications based on the knowledge of a biological target
Define drug re-purposing
Drug repurposing or repositioning is a technique whereby existing drugs are used to treat emerging and challenging diseases
Define adverse drug reaction
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug
Side effect vs Adverse drug reaction
Side effect
- unintended effect of a drug due to pharmacological properties but can be BENEFICIAL
ADR
- Always NEGATIVE
What are the 3 types of effects of ADR’s?
- Toxic effect (beyond therapeutic range)
- Collateral effects (therapeutic range)
- Hyper-susceptibility effects (below therapeutic range)
What are some reasons for toxic effects?
- dose is too high
- drug excretion reduced by impaired renal or hepatic function
- interaction with other drugs
What are the causes of collateral drug effects?
- standard therapeutic doses
- beta blockers causing bronchoconstriction
An example of a hypersusceptibility reaction?
Anaphylaxis and penicillin allergy
What are risk factors for ADRs?
- Female
- elderly
- neonates
- polypharmacy
- genetic predisposition
- hypersensitivity/allergies
- hepatic/renal impairment
- adherence problems
What are drug risk factors for ADRs?
- steep dose response curve
- low therapeutic index
- commonly cause ADR’s
What are some causes for ADR’s?
- Pharmaceutical variation—eosinophilia-myalgia syndrome with L-tryptophan
- Receptor abnormality—malignant hyperthermia with general anaesthetics
- Abnormal biological system unmasked by drug—primaquine induced haemolysis in patients deficient in glucose 6-phosphate dehydrogenase
- Abnormalities in drug metabolism—isoniazid induced peripheral neuropathy in people deficient in the enzyme N-acetyl transferase (that is, those who are slow acetylators)
- Immunological—penicillin induced anaphylaxis
- Drug-drug interactions—increased incidence of hepatitis when isoniazid is prescribed with rifampicin
- Multifactorial—halothane hepatitis
What are the 6 types of time dependant reactions?
- Rapid reactions
- First dose reactions
- Early reactions
- Immediate reactions
- Late reactions - e.g, seizures on withdrawal
- Delayed reactions - pregnancy
What are the 5 types of adverse drug reactions?
- Augmented
- Bizarre
- Chronic
- Delayed
- End of use
ABCDE
What is a type A adverse drug reactions?
Augmented
- predictable
- dose dependent
- common
- increase of normal side effects you would expect
- high morbidity, low mortality
e.g. drug abuse, overdose
Type B
Bizarre
- Not predictable
- Not dose dependent
- life threatening
- can be allergy or hypersensitivity
- low morbidity, high mortality
(anaphylaxis)
Type C
Chronic / continuous
- uncommon
- related to cumulative dose
- time related
e.g. osteoporosis and steroids
colonic dysfunction due to laxatives
Type D
Delayed
- uncommon
- usually dose related
- shows itself some time after the use of the drug
- malignancies after immunosupression
e.g. in pregnancy only have effect later - thalidomide
Type E
End of treatment
- uncommon
- occur after abrupt drug withdrawal
e.g. opiate withdrawal syndrome
Type F
Failure of therapy
- common
- dose related
- often caused by drug interaction
e.g. failure of oral contraceptive in presence of enzyme inducer
Which are the most common drugs to have ADR’s?
Antibiotics
Anti-neoplastics
Cardiovascular drugs
Hypoglycaemics
NSAIDS
CNS drugs
Which body systems are most commonly affected?
GI
Renal
Haemorrhagic
Metabolic
Endocrine
Dermatologic
What is the MHRA?
Medicines and healthcare products regulatory agency
- responsible for approving medicines and devices for use
What is the yellow card scheme?
- 1964
- ADR reporting scheme
- collects spontaneous reports and suspect ADR’s
- voluntary scheme
Why report ADRs?
- Important for patient safety
- To identify ADRs not identified in clinical trials
- To identify new ADRs ASAP
- To compare drugs in the same therapeutic class
- To identify ADRs in ‘at risk’ groups
What to report on a yellow card?
All suspected reactions for:
- herbal medicines
- black triangle drug (a medicine undergoing ‘additional monitoring’)
All serious suspected reactions for
- established drugs, vaccines, and contrast media
- drug interactions
Define hypersensitivity.
reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects
immunologic (allergic) or non-immunological mechanisms
What are risk factors for hypersensitivity?
Medicine factors:
- protein or polysaccharide based macro molecules
Host factors:
- females
- HIV
- prep drug reactions
- uncontrolled asthma
Genetic:
- certain HLA groups
- acetylator status
How is adrenaline useful in anaphylaxis?
- vasoconstriction - increase BP, increase in peripheral vascular resistance
- Stimulation of beta 1-adrenoceptors
- Reduces oedema and bronchodilates (beta 2)
- attenuates further release of mediators from mast cells
Which vitamin has a reverse effect on warfarin?
Vitamin K - reverses anticoagulation
How does a salbutamol inhaler act on the body to help with asthma?
Relaxes bronchial smooth muscle cells
What effect does a alpha 1 antagonist have on blood vessels?
Dilation of venous capacitance vessels
What characteristics should an anaesthetic drug have in terms of its protein binding and lipid solubility?
Low protein binding
- so higher conc of the drug is free in the plasma enabling it to have an effect
- when bound to proteins the drug cannot work
High Lipid solubility
- can readily cross the blood brain barrier (contains phospholipids) and reach its site of action in the brain
Why is morphine bad for someone with renal failure?
Morphine is metabolised in the liver by CYP2D6 enzymes to Morphine-6-glucuronide
- this is more potent than morphine and needs to be readily excreted from the kidney
- if a patient has renal failure, this cannot be excreted so a lower dose of morphine needs to be given
