Pharmacology Flashcards
What is pharmacodynamics
how the drug affects the body
What is pharmacokinetics
the distribution of a compound within the organism, according to it’s ADME (absorption, distribution, metabolism, excretion)
What is ‘druggability’
The ability of a protein to bind small molecules with high affinity (10-15% of the genome)
Define receptor
Component of a cell which interacts with a ligand and initiates a chain of biochemical events leading to the ligands observed effects
Define neurotransmitter
small molecular mass molecule associated with transmitting a neural response
Define autacoids
molecules associated with transmitting a signal locally eg histmaine or cytokines
Define hormones
molecules which transmit a biological signal from one cell to another elsewhere in the body, using the blood
Name an example of a ligand gated ion channel
Nicotinic ACh
Name an example of a G protein coupled receptor
Beta adrenoceptor
Name an example of a kinase linked receptor
Growth factor receptor
Name an example of a cytosolic receptor
Steroid hormone receptor
Which conformational state is the receptor in when the G protein binds GDP
Open
Which conformational state is the receptor in when the G protein binds GTP
Closed
What is a heterogenic G protein coupled receptor
One which binds to two different molecules
Muscarinic (M3) receptors are associated which protein, enzyme and second mesengers
Gq, phospholipase c, IP3/DAG
Adrenergic (B2) receptors are associated with which protein, enzyme and second messengers
Gs, adenly cyclase and cyclic AMP
What is needed to activate a kinase linked receptor
A ligand in dimer form
What is the function of zinc fingers in nuclear receptors
As part of the DNA binding domain they identify DNA motifs
Which disease is caused by loss of ACh receptors
Myasthenia Gravis
Which disease is caused by an increase in ckit receptors
Mastocytosis
Agonist definition
A compound which binds to a receptor and activates it
Antagonist definition
A compound which reduces the effect of an agonist
What shape is the agonist response curve on a linear scale
Logarithmic
What shape is the agonist response curve on a log scale
Sigmoidal
What is EC50
The concentration which gives half the maximal response and achieves potency
What is efficacy (Emax)
The maximum response achievable from a dose
What is a partial agonist
A drug which binds to a receptor but only has partial efficacy relative to a full agonist
How can you classify receptors
using competitive antagonists or agonists which a range of potencies
What is the antagonist to the nAChR receptor
Atropine
What is the antagonist to the mAChR receptor
Curare
What are H1 receptors associated with
Allergy
What are H2 receptors associated with
Gastric acid secretion
What is a H2 antagonist and its role
mepyramine and it causes ileum relaxation and has no affect on parietal cells
What is a H2 agonist and its role
histamine and it causes ileum contraction and acid secretion from parietal cells
What are H3 receptors associated with
CNS disorders
What are H4 receptors associated with
Immune systema nd inflammatory responses
Define affinity
Describes how well a ligand binds to a receptor
Define efficacy
Describes how well a ligand activates a receptor
What are tissue related factors which affect drug action
Signal amplification and receptor number
What is the affinity and efficacy of a succesful competitive antagonist
Affinity must be equal or better than the agonist and efficacy is zero
What is the functional reserve of a receptor
The number of receptors free when maximal response is acheived
What is an inverse agonist
An agent which deactivates a receptor
What is the name of the primary receptor site
Arthosteric site
What is the action of an agonist
To cause activation of a receptor
What is the action of an antagonist
To prevent activation of a receptor
What is the action of an invesrse agonist
To cause deactivation of a receptor
Define tolerance
A reduction in the drug agonist effect over time after continuously repeated high doses
What is an enzyme inhibitor
A molecule which binds to an enzyme and reduces its activity
Active transport definition
The movement of a molecule across a membrane, from an area of low to high concentration using energy
What is fureosemide
a loop diuretic which targets NKCC symporters in the ascending tubule. Causes sodium, pottasium and chloride loss
Which ion channels are involved in the treatment of heart failure
Epithelium sodium
Which ion channels are involved in the treatment of nerve arrythmia
Voltage gated calcium/sodium
Which ion channels are involved in the treatment of diabetes
metabolic pottasium
Which ion channels are involved in the treatment of epilepsy
Receptor activated chloride
Which antihypertensive targets transmembrane sodium channels
Amiloride
Name an angioselective calcium channel blocker
Amlodipine
Define action potential
A momentary change in electrical potential on the surface of a cell, which occurs when it is stimulated and results in transmission of an electrical impulse
Name an antiarrythmic drug which acts by blocking sodium channels and action potentials
Lidocaine
What are the three possible states of a voltage gated sodium and pottasium channel
Open, Closed, Innactivated
Name type 2 diabetes drugs which block pottasium channels causing insulin release
Repaglinide and nateglinide
What is an ionotropic receptor
A receptor directly linked to an ion channel
What is the role of barbiturates
Increase the permeability of the channel to chloride
How does digoxin treat AF, HF and atrial flutter
It inhibits Na/K ATPases, this increase cardiac Na and therefore Ca levels, increasing the length of the cardiac action potential and reducing heart rate
What is a heterodimeric protein and name an example
A protein which is the product of two genes such as Gastric K/H ATPase
Name an irreversible cholinesterase inhibitor and where it is found
Organophosphates, found in insecticides and nerve gases
Define xenobiotics
Compounds foreign to an organisms biochemistry such as any drug or poison
Define absorption
Process of transfer from the site of administration into the general or systemic circulation
Name 4 ways a drug can pass through a membrane
Passive diffusion through lipid layer, diffusion through pores or channels, carrier mediated processes, pinocytosis
Define carrier mediated transport
Carries molecules against their concentration gradient into cells using ATP
What is Verpamil
A Pgp inhibitor, increases concentration of anticancer drugs in cytoplasm and therefore increases their action
What is Probenecid
A OAT1 inhibitor, increases uric acid (and penicillin) secretion in urine
Define pinocytosis
Intake of small droplets of fluid by a cell by cytoplasmic engulfment
Name a drug which is a weak acid
Aspirin
Name a drug which is a weak base
Propanolol
What two factors determine the ionisation of a drug
The strength of the ionised groups, the pH of the solution
Which ionisation extent is more lipid soluble
Less ionised
What is pKA
The ionisation constant, the point at which 50% are ionised
Where are weak acids best absorbed
An acidic environment, eg the stomach
Where are weak bases best absorbed
A basic environment, eg the intestines
What is useful about olsalazine’s structure
As it is highly polarised it is only partially absorbed in the small intestine, so can pass to the colon and treat IBD
What factors increase the rate of gastric emptying
Gastric surgery
What factors decrease the rate of gastric emptying
Food, trauma or drugs (Antimuscarinics - oxybutinin)
What causes poor absorption of a drug from the small intestine
Short gut syndrome
What are the four barriers an orally taken drug must pass
IILL. Intestinal lumen, intestinal wall, liver, lungs
How does the lumenal wall limit absorption
Lumenal enterocytes have efflux transporters which transport drugs back into the lumen
How can you avoid the livers metabolism
Deliver the drug to part of the GI tract which isnt drained by the splanchnic circulation such as the mouth or rectum
Which absorption routes have a 1 minute absorption time
IV and interosseous
Which absorption routes have a 3 minute absorption time
Endotracheal and inhalation
What is the sublingual route absorption time
3-5 minutes
Which absorption routes have an absorption time of around 30 minutes
Intramuscular, subcutaneous, rectal, ingestion and transdermal
When is the intraosseous route used
In paediatric trauma where the IV is hard to find
What are the 3 criterion of a transcutaneous drug
Lipid soluble, potent and not an irritant
What factors cause increased removal of a drug from an IM site
Increased blood flow or water solubility
What is a depot
A slow acting store of lipophilic formulation, given intramuscularly it is useful in patients with poor compliance
What are the disadvantages of inhalation as a route of administration
Risk of alveolar toxicity and non volatile drugs must be given as aerosols or dry powders
Which drugs easily pass through the BBB
Lipid soluble
Define distribution
Process by which a drug is reversibly transferred from the general circulation to the tissues, dependent on a concentration gradient out of the blood
Which organs are well perfused and will therefore receive a high dose more quickly
Brain, liver, lungs
Define bolus
A large dose of a drug administered by rapid injection rather than infusion
Define first order kinetics
Exponential decline in concentration, a constant fraction of the drug is eliminated per unit time
Define zero order kinetics
Rate of removal is constant and unaffected by changes in concentration; seen in saturated enzyme systems
Define half life
Time taken for a concentration to reduce by one half
Define bioavailability
The fraction of the administered drug which reaches the systemic circulation unaltered
Define distribution
Rate and extent of drug movement into and out of tissues from the blood
What determines distribution of water soluble drugs
The rate of passage across membranes
What determines distribution of lipid soluble drugs
The rate of blood flow to tissues accumulating the drug
What is volume distribution
Total amount of drug in the body (dose)/plasma concentration
(amount needed to have dose in plasma)
Define clearance
The volume of blood or plasma cleared of a drug per unit time
Define steady state (Css)
Equilibrium between drug input and elimination
How do you shorten the time taken to reach steady state in drugs with a long half life
By giving a loading dose
Why is intraoccular pressure controlled
To prevent glaucoma causing blindness
Why is airway tone controlled
To prevent bronchospasm (constriction)
Which output from the CNS to the body isnt controlled by the autonomic nervous system
Skeletal muscle control
Which CNS nerve has a role in the innate immune system
Vagus
Define enteric nervous system
part of the peripheral nervous system, a plexus of nerves around the gut
Define somatic
One neurone comes from the CNS to innervate muscle
Where are parasympathetic nerve ganglia
Near the target organ
Where are sympathetic nerve ganglia
Near the spinal cord
What is the sarcral outflow
Parasympathetic, innervates pelvis and does contain some sympathetic
Parasympathetic neurotransmitter and receptor at tissues
ACh and muscarinic
Sympathetic neurotransmitter and receptor at tissues
Noradrenaline and adrenergic
Which organs only have sympathetic innervation
Blood vessels and sweat glands
Which organs only have parasympathetic innervation
Bronchial smooth muscle and the eye
Which organs have both sympathetic and parasympathetic innervation
Heart, gut, bladder
Parasympathetic neurotransmitter and receptor at ganglion
ACh and Nicotinic
Sympathetic neurotransmitter and receptor at ganglion
ACh and nicotinic
Parasympathetic NANC post ganglionic substances
NO, Vasoactive Intestinal Peptide
Sympathetic NANC post ganglionic substances
ATP and neuropeptide Y
Where are M1 receptors found
The brain
Where are M2 receptors found
The heart
Where are M3 receptors found
Glandular and smooth muscle
Where are M4 receptors found
The CNS
Where are M5 receptors found
The CNS
What is glaucoma
Increased intraoccular pressure results in nerve fibre loss from the optic nerve
What is ipratropium bromide (atrovent)
SAMA to M3 for bronchoconstriction
What is tiortropium
LAMA to M3 for bronchoconstriction
Name uses of anticholinergics/antimuscarinics
Bronchoconstriction, overactive bladder, dilate eye for examination, Intestinal and bowel spasms, raise heart rate
Name roles of Acetylcholine outside the autonomic nervous system
Memory and sickness
What causes ACh defecit
Botulin toxin release, nicotinic blockers, myasthenia gravis
What are nicotinic blockers
Given in surgery to relax muscles, pancuronium and suxamethonium
What are consequences of ACh defecit
Bad memory, confusion, constipation, drying, worsening of glaucoma and blurred vision
What are causes of ACh surplus
Organophosphate insecticides and nerve gases are irreversible insecticide inhibitors
What are consequences of ACh surplus
Muscle paralysis and twitching, salivation, confusion, adaption and desensitivity to high levels
Which protein is associated with alpha 1 adrenoceptors and what is it’s affect
Gs, increases intracellular calcium
Which protein is associated with alpha 2 adrenoceptors and what is it’s affect
Gi, inhibits cAMP generation
What is the effect of alpha 1 adrenoceptor activation
vasoconstriction especially in the skin and splanchnic beds
Where are alpha 1 adrenoceptors agonists used
For septic shock and topically for nasal decongestion
Where are alpha 1 adrenoceptor antagonists usead
To lower BP, targetting alpha 1A can be used to treat hypertrophic prostate
Name an alpha 2 agonist and its effects
Clonidine, lowers BP treats ADHD and anxiety
What affects do beta 1 adrenoceptors have
Increased chronotropic (rate) and inotropic (strength) effects on the heart
What is the affect of Beta 2 adrenoceptor activation
Relaxes smooth muscle, bronchodilation, delay of laboiur
what is the affect of beta 3 adrenoceptor activation
enhanced lipolysis and bladder detrusor relaxation, used to alleviate overactive bladder symptoms
Which adrenoceptors are involved in lipid and carbohydrate metabolism
Beta 1 and 3 (2 surpresses awareness)
Which receptors does propanolol act on
Both Beta 1 and 2
Which receptors does atenolol act on
Just Beta 1
Name some beta blocker side effects
tiredness, cold extremities, bronchoconstriction, bradycardia, hypoglycaemia and cardiac depression
What is preeclampsia
pregnancy induced hypertension with proteinuria (and/or oedema)
What is methyldopa and how does it work
last resort hypertensive used in preeclampsia which blocks noradrenaline synthesis
What are MAOIs and how do they work
Monoamine oxidase inhibitors, are antidepressants which prevent NAd breakdown
Which adrenoceptors are influenced in COPD management
M3 antagonist, B2 agonist
Which adrenoceptors are influenced in bladder instability management
B3 agonist
Which adrenoceptors are influenced in cardiac disease (angina, AF) management
B1 blocker
Which adrenoceptors are influenced in pneumonia management
NAd, septic shock. B2 agonist for wheeze
Which adrenoceptors are influened in anaphylaxis treatment
Adrenaline
Which adrenoceptors are influenced in cardiac arrest treatment
Atropine (nAChR antagonist) for bradycardia
Name some naturally occuring opioids
Morphine and codeine(weak)
Name some chemical modifications of natural opioids
Diamorphine, oxycodeine, dihydrocodeine
Name some synthetic opioids
Pethidine and fentanyl
Name an opioid antagonist
Naloxone
When are slow release opioids given
Bidaily in palliative care
Name some morphine side effects
Sedation and respiratory depression
What does the term parenteral mean
Bypasses the mouth and gut
Define potency
A measure of drug activity, expressed in terms of the amount required to produce an effect of given intensity
Define tolerance
A reduction or loss of the normal response to a drug or other substance that usually provokes a reaction in the body
Define dependence
The physical or psychological effects produced by the habitual taking of certain drugs - characterised by a compulsion to continue taking the drug
What are endorphins
endogenous morphines which are involved in the fight or flight response
What are enkephalins
point to point peptide messengers
Why are there problems with opioids
They were designed for the fight or flight response, not sustained activation and there are therefore problems with tolerance and addiction
What are the four types of opioid receptor
Mu opiate peptide, Kappa opiate peptide, Delta opiate peptide, Noiceptin opiate peptide
What is the first way opioids inhibit pain
inhibit action potential generation at noiceptive afferents
What is the second way opioids inhibit pain
Inhibit transmission of pain in the dorsal horn
What is the third way opioids inhibit pain
Inhibit descending GABA release from interneurons in periaqueductal grey
What is another way opioids inhibit pain
Influence the cortex, changing emotional interpretation of pain
Should you give lumbar puncture epidural opiates
They give precise treatment but opiates need to work on the brainstem too so must be given systemically
Why shouldnt opioids be given in chronic non cancer pain
As the opioids lose their effectiveness within weeks
Whats the difference between prescribed and drug dealer opiates
Drug dealers use much more potent derivatives which are highly toxic
Which enzyme is involved in the bioactivation of codeine and tramadol
CYP2D6
Why should you be careful about prescribing codeine
CYP2D6. 10-15% caucasians have reduced action, 10% of these are lacking the enzyme. 5% have overactive
When should you be careful about prescribing tramadol
To those on antidepressents, as it inhibits Serotonin and Noradrenaline reuptake, so interacts with SSRIs, MAOIs and tricyclic antidepressants
When should you be careful about prescribing morpheine
In those with renal function below 30%, as the more potent metabolite (morpheine 6 glucorinide) will build up
What is a teratogen
agent which causes disturbance to the development of foetus
Define antibiotic
An agent produced by microorganisms that kills or inhibits the growth of other microorganisms in high dilution
What is the MIC
Minimum inhbitory concentration, the concentration required of a bacteriostatic antibiotic to get no microbial growth (determined using increasing turbidities, in reality the antibiotic must occupy the sites and for long enough)
Which antibiotic is good for staphylococcus
Flucoxacillin
Which antibiotics show concentration dependent killing and what is it
Aminoglycosides and quinolones, peak concentration/MIC ratio key parameter
Which antibiotics show time dependent killing and it is it
Beta lactams, macrolides and oxazolidonones. Time spent above MIC most important
Name some penicillins, what do they do and when are they used
Amoxicillin, coamoxiclav, target peptidoglycan in cell walls and are used in pneumonia and UTI
What is vancomycin
A glycopeptide, targets gram positive and used in endocarditis, osteomylitis or antibiotic associated colitis (C. dificile)
What are polymyxins
Polymixin B has a toxic effect of bacterial cell membranes, used against gram negative in E Coli and P Aerguinosa infection
What are trimethopims
Trimethoprim is a folate antagonist and is used against gran negative bacteria in UTIs
What are fluroquinolones
Ciprofloxacin targets bacterial topoisomerase and is primarily used against p aerguinosa and second line for UTI, GI and LRTIs
What is rifampicin
Targets RNA polymerase, used to treat TB, leprosy and legionairres
What are aminoglycosides
Gentamycin targets protein synthesis in Gram negative aerobes, used in severe sepsis, endocarditis, pyelonephritis and complex UTIs
What are macrolides
Erythromycin and clarithromycin inhibit protein synthesis and are used in respiratory, soft tissue and skin infections (with other drugs for pneumonia and H pylori)
What is clindomycin
Targets protein synthesis, using in the treatment of necrosing fascitis as it counters gram positive toxins. Also used in cellulitis of penicillin allergens
What are tetracyclines
Doxycycline blocks protein synthesis and is used in the treatment of skin conditions, atypical pneumonias and chlamydial infection (pelvic inflammatory disease)
Define adverse drug reaction
An unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected
Define primary adverse effect
Consequence of the drug’s primary pharmacological effect (Beta blockers causing heart block and bradykinia)
Define secondary adverse effect
accessory to the intended therapeutic consequences of drug adminitstration (Beta blockers causing bronchospasm)
What is a side effect
A reaction from a dose within the therapeutic range
What is a toxic effect
A reaction from a dose beyond the therapeutic range
What is a hyper susceptibility effect
A reaction from a dose blow the therapeutic range
What are the symptoms of Cushings disease
Moon face, central obesity and skin features
What is pinocomelia and what causes it
Hands and feet close to the trunk, caused by thalidomide in first trimester
Name three common ADRs
Pencillin allergy (ranging from rash to anaphylaxis), insulin as a hypoglycaemic and NSAIDS affecting kidneys
What are patient risks in ADRs
Female, elderly (or neonate), genes, renal/hepatic failure, poor adherence, polypharmacy, atopy
What are the drug risks in ADRs
Steep dose response curve, low therapeutic index and a common cause of ADRs
What are prescriber risks of ADRs
Rushed, knowledge gaps, mistakes, wrong route or direction
What are black triangle drugs
Drugs which are undergoing additional monitoring
What is considered a serious reaction
Fatal, life threatening, disabling, results or prolongs hospitalization
Penecillin allergy is an example of which type of hypersensitivity
Type 1
How does adrenaline stop the release of inflammatory mediators from mast cells and basophils, in anaphylaxis treatment
Increases the intracellular cAMP
Define drug interaction
A change in a drug’s effect on the body when the drug is taken with a second drug
Define drug synergy
The drugs work together to create a greater overall effect
Define drug antagonism
The addition of a drug, works against the first drug and decreases the overall effect
What is the meaning of narrow therapeutic index
A fine line between therapeutic and harmful effect
Which drugs increase the motility of oral contraceptive pills
antibiotics
Patients weighing less than what weight should be given half the noramal dose
50kg
Which enzyme does ginger effect
Increased thromboxane synthetase
Why does grapefruit juice affect drugs
Affects CYP3A4 and increases bioavailability, and potentiates potential side effects
Which drugs interact with grapefruit juice
Antiarrythmic, antihistamines, Ca2+ antagonists, statins and immunosurpressants
Which are drugs are weak bases
Pain killers and warfarin
Warfarin shouldnt be prescribed with
erythromycin, clarithromycin, tramadol and amiodorone
SSRIs shouldnt be prescribed with
tricyclic antidepressants and tramadol
What is rhabdomyolysis
Rapid breakdown of skeletal muscle following injury
Interactions with which drug can cause bleeding
Warfarin
Interactions with which drug can cause rhabdomyolysis
Simvastatin
Interactions with which drug can cause serotonin syndrome
SSRIs
Interactions with which drugs can cause renal failure
NSAIDs or Cox2 inhibitors, ACE inhibitors and dehydration or furosemide
Define patient compliance
The extent to which the patient’s behaviour (in terms of taking medications, following diets or other lifestyle changes) coincides with medical or health advice
What is the necessity-concerns framework
The two categories why patients dont take drugs: Necessity beliefs (perceptions of the personal need for treatment) and concerns (about a range of potential adverse consequences)
What is the theory of concordance
A consultation is a negotiation between equals, there is a therapeutic alliance with openness, reality and respect for the patient’s agenda
What is antibiotic stewardship
The systematic education of prescribes to follow evidence based prescribing to reduce antibiotic overuse and therefore antibiotic resistance
What are the four ways bacteria develop resistance
Change antibiotic target site, destroy antibiotic, prevent antibiotic access, remove antibiotic from bacterial membrane
Define substance use
Ingestion of a substance affecting the CNS which leads to behavioural and psychological changes. Implicitly non therapeutic changes
Define acute intoxication
Disturbances in the level of consciousness, cognition, perception, behaviour, affect and other psychophysiological responses and functions
Define at risk (hazardous) drinking
a pattern of drinking which brings about the risk of physical or psychological harm - screening tools
Alcohol abuse (harmful) drinking
A pattern of drinking which is likely to cause physical or psychological harm
Define substance abuse
A set of behavioural, cognitive and physiological responses that can develop after repeated substance use
Define acquired resistance
Bacteria which was previously susceptible obtains the ability to resist the activity of a particular antibiotic
What is conjugation
Sharing of extrachromosomal DNA plasmids via a sec pillus
What is transduction
Bacteriophages carry donor bacterium DNA in a virus particle to a recipeint bacterium during infection
What is transformation
Free DNA is taken up from the environment and incorporated into their chromosome
Which antibiotics are used as a last resort
Carbapenams - primaxin
Define stereoisomer
Same molecular formula and sequence of bonded atoms but differ in three dimensional orientations and their atoms in space
Which element is commonly used in anticancer drugs
Platinum
What are monoclonal antibodies
-mab, all have specificity to the same epitope
What is infliximab
MAB which targets TNF alpha and is used to treat autoimmune disease. By extracellular neutralisation and inhibits lymphocyte proliferation
What are murine antibodies and their suffix
mice omab
What are chimeric antibodies and their suffix
from a mix of organisms, ximab
What are humanized antibodies’ suffix
zumab
What is the human antibody suffix
umab
What is the brambell receptor
Intestinal FCRN receptor for orally absorption of antibodies form breast milk in the neonate
wWhat are FCRN receptors
Systemic receptors which absorb IgG into cells protecting them from metabolism
Is IgG filtered by the kidneys
No, 150kD
Name three drugs sourced from animals
Insulin, thyroxine and steroids
How is insulin prescribed
In units which are based on hypoglycaemic activity in rabbits, 25units/mg
What does mitogenic mean
Triggers mitosis
How does shorter acting insulin work
Insulin lipro turns on lyseine and proline residues preventing insulin dimer/hexamer formation
How does long acting insulin work
Can bind to albumin and insuline glargine fors aggregats in ECF at neutral pH
What is cachexia
Wastage of tissue
Name recombinant proteins in clinical use
Insulin, EPO, GH, IL, gamma interferon, IL-1 receptor agonist
Mineralocorticoid adverse effects
HTN, fluid retention, K+ loss, Ca2+ loss
Glucocorticoids adverse effects
Diabetes, cushings syndrome, osteoporosis, muscle wasting, peptic ulcer
What is pathogenicity
Ability to cause disease
What is immunogenicity
Ability to provoke an immune response
