Pharmacology Flashcards
What is pharmacology? What is pharmokinetics? What is pharmocodynamics? What does physiochemical mean? What is a drug?
The study of the effects of drugs
How the body affects the drug; absorption, distribution, metabolism and excretion (ADME)
How the drug affects the body
The way in which drugs interact with each other
Any compound that is administered with an intended therapeutic effect
The 3 pharmacokinetic phases of drug uptake? Most pharmacodynamic theory in terms of what? For a dissolved drug in the plasma, what is meant by a first order process? Rate of diffusion is directly proportional to what too?
Uptake into the plasma, distribution from the plasma, elimination from the plasma
Conc times curves
Rate of diffusion= directly proportional to the conc gradient
Temperature- most drugs won’t work outside normal physiological temperature
What does second, third and zero order also mean? Diffusion is a what function?
Rate is directly proportional to the square of the conc of the drug
Proportional to the cube of drug conc
Zero order= rate is unrelated to conc of drug
Exponential function- rate of reaction is governed by one of the components involved in the reaction whose quantity/ magnitude is changing
What is the plasma? Proteins are found here as result of what? pH of what is reflected in the plasma? pH of plasma compared to interstitium?
The fluid fraction/ aqueous solution that remains when cells are removed from the blood
Polar amino acid side chains
The interstitium
Higher due to diffusion gradient
3 main compartments divided by tissue lipid rich barriers in pharmacokinetic theory? What is the ‘‘cellular tissue’’ divided into? 5 ways drug can move from its site of administration to its target?
Plasma (5 litres,) interstitial (15 litres) and intracellular (45 litres)
Vessel rich viscera- muscle tissue
Vessel poor- fat stores/ subcutaneous tissue
Simple diffusion, facilitated diffusion, active transport, through extracellular spaces, non ionic diffusion
What process is active transport at initially but then when saturated? What cannot enter through pores in extracellular spaces? How does non-ionic diffusion work? When pH is increased, weak acid/ base more/ less ionised?
First order, then zero order when becomes saturated
Protein
Ionic molecule= less ionic, can cross lipid membrane to enter the cell e.g. aspirin
Weak acid= more ionised, weak base= less ionised
What has large effect on uptake into plasma? What is bioavailability? Routes of administration?
Route of administration
Amount of drug taken up as proportion of amount administered
Oral, intramuscular, intravenous, transcutaneous, intrathecal(into CSF,) sublingual, inhalation, topical, rectal
What route has greatest variability and why? Most tablets are either what? Water soluble tablets will not pass across cell membranes unless there is what?
Oral- due to different factors involved; surface area of gut, diarrhoea, pH of gut (alkaline at duodenum)
Weak acids or weak bases
Carrier mediated transport
Bioavailability of intramuscular, IV and transcutaneous? Aspirin in the stomach? In plasma? Antacids do what? Ingesting what increases pH? What reduces aspirin uptake from stomach?
Close to 1, should be 1, lower than IV
Is acidic, so dissolves, becomes less ionised, moves rapidly across gut due to un-ionised
More ionised due to higher pH
Act to increase pH e.g. omeprazole and ranitidine act to reduce acid secretion in stomach and increase pH
Alkali foods
Raised pH–> reduced bioavailability
Drug is distributed in plasma according to what? What are found in the aqueous phase? What are only active in the plasma compartment? What are active in plasma and interstitial compartment? What are only active in the intracellular fluid?
Its chemical properties and molecular size
Dissolved gases and small ionic molecules
Proteins/ large molecules
Water soluble molecules
Lipid soluble molecules
What is a steady state? How is volume of distribution calculated? What is it?
Where drug intake is in equilibrium with its elimination
Total amount of drug in body/ conc of drug in plasma
The volume that drug would occupy if it was distributed through all compartments as if they were all plasma
Why may volume of distribution be larger than it actually is? Vd of highly lipid soluble drugs and enter what?
When calculating, concentration and volume is taken from plasma- when drug infected, can be taken up by organ systems, so blood conc will decrease
High volume of distribution and enter the CNS
3 things found in plasma? In interstitial fluid? 6 in intracellular? Vd of amiodarone?
Plasma expanders, immunoglobulin, warfarin
Aspirin/ other NSAIDs, antibiotics, muscle relaxants
Steroids, local anaesthetics, opioids, CNS drugs, paracetamol, amiodarone- 450L, very easily taken up by tissue
What does compartment modelling assume? Shows plasma conc against what during when? Line of best fit to what? For every compartment, what is added?
That plasma is in equilibrium
Against time during distribution of drug phase
To 1,2 or 3 compartment models of distribution
Another C0e-kt
Most lipid soluble drugs have how many compartment models? Elimination of drug is from what compartment? What 2 routes are for vast majority of drugs? What process type?
3- suggests movement is plasma–> viscera–> adipose tissue
Plasma
Renal and/ or hepatic elimination
First order process
2 definitions of clearance? Both are measures of what? Can influence rate of elimination how? Units?
Removal of drug from plasma by liver/ kidney
Volume of plasma that can be completely cleared of drug per unit time
Rate at which plasma drug is eliminated per unit plasma conc
Efficiency
Depending on plasma conc of drug
Mls minute-1 (ml/ min)
All factors affecting what affect clearance? How are water soluble molecules eliminated? Larger can be eliminated how?
Renal blood flow- notably blood pressure
Which pass through glomerular endothelia= eliminated by glomerular filtration
By active tubular secretion
Calculation of rate of elimination assumes what? What is assumed to be constant? Clearance=? What is used as a marker substance in the kidney?
Rate of elimination= rate of appearance in urine
Plasma conc during clearance= constant
Rate of appearance in urine/ plasma conc
Creatinine
Renal blood flow= what % of cardiac output and value? Renal plasma flow= what % of blood flow? Glomerular filtration= what % of renal blood flow?
18%= 1 L/min 60%= 600mls/ min 12%= 130ml/ min
Many drugs are eliminated by the kidney by either what? Highly lipid soluble are metabolised how? What drugs have little exposure to renal clearance?
Glomerular filtration e.g. digoxin and gentamicin/ active secretion e.g. penicillin, furosemide, thiazides
Metabolised to water soluble glucuronic acid conjugates–> actively secreted e.g. morphine 3 and 6 glucuronides
Highly protein bound drugs
Acute and chronic renal impairment due to what? Drugs for patients with renal impairment? Hypoalbuminaemia results in what?
Acute= secondary to reduced pre-renal perfusion
Chronic= diabetes and hypertension
Ones eliminated by liver instead
Lipid soluble drugs= highly freely diffusible fractions and greater effects
Elevated plasma creatinine and urea compete for what? Management of renal impairment?
For lipid binding sites on protein and displace more lipid soluble free drug
Avoid nephrotoxic drugs, make corrections based on plasma creatinine- estimate % reduction in clearance and then alter dose, measure plasma cones if toxicity risk
Hepatic blood flow= % of cardiac output? All hepatic clearance involves what? Active secretion from where to where if what?
24%- 3/4 from portal vein, 1/4 from hepatic artery
Active transport
Liver–> bile duct if water soluble
What is the hepatic excretion ratio (HER)? High HER so clearance only limited by what? Low HER so clearance only limited by what? What can alter HER?
Proportion of drug removed by 1 passage through the liver
Hepatic blood flow
Diffusion
Liver enzymes
Liver does what if exposed to low HER drug? Effect of high HER drugs? Described as having a high what?
Produces more enzymes to enable it to increase clearance
Have little effect on number of new enzymes
First pass metabolism- first go to liver before can reach its target, but by then most of it will have been eliminated, limited uptake from oral administration
What is a pro-drug? 95% phase 1 reactions are where? Involves? Known as what? Mainly catalysed by what?
Activated in the liver, cleaved into the active drug via metabolism e.g. hydrocortisone–> cortisol
In liver SER- introduce/ expose hydroxyl group and reactive group for conjugation
Functionalisation- small increase in hydrophilicity
By cytochrome P450 enzymes
Cytochrome P450 uses what to oxidise substances? Requires what? E.g. drugs inhibit cytochrome P450?
Fe2+ group
Energy and molecular oxygen
Amiodarone and cimetidine
Phase II conjugation also known as what? Involves? Uses what enzyme? Co-enzyme needed to conjugate glucuronic acid?Forms what bonds?
Glucuronidation Adds glucuronic acid- more hydrophilic Glucuronosyltransferase UDPGA Covalent bonds--> glucuronides
Phase 1 water soluble metabolites and phase 2 glucuronides enter what? Enters what during cholestasis and reduced renal function?
Bile and gut via cystic duct, some I and II= blood and excreted in urine
Increased by kidneys/ biliary secretion
How can enterohepatic circulation prolong action of some drugs? What risk? Minimal effect on drug metabolism until what % of liver if not functioning? Pharmacodynamic alterations= often due to what?
Large bowel flora= metabolise glucuronic acid on phase II–> re-diffuse from gut into blood and have prolonged effect before going back to liver to be re-conjugated and excreted again
Drug accumulation and toxicity
70%
Secondary to disease
Drugs with active metabolites? 5 main types of drug targets?
Prednisone, isosorbide denigrate, codeine, diamorphine, L-dopa, cortisone, morphine
Receptors, enzymes, transporters, ion channels, most= proteins
3 methods of chemical communication? What is a receptor? Can be either what? 4 types of receptors?
Neurotransmitters- Ach, serotonin
Autoacids; cytokines, histamine
Hormones; testosterone, hydrocortisone
Component of cell that interacts with specific ligand and initiates change of biochemical events–> ligands observed effects
Exogenous (drugs) or endogenous (hormones, neurotransmitters)
Ligand-gated ion channels, G protein coupled receptors, kinase- linked receptors, cytosolic/ nuclear receptors
E.g. of ligand-gated? E.g. of G-protein coupled? Kinase-linked? Cytosolic/ nuclear receptors?
Nicotinic Ach receptor
Beta-adrenoreceptors- serpent-like receptors
Receptors for growth factors- show intrinsic kinase activity, tyrosine phosphorylation
Steroid receptors- can modify gene transcription, zinc fingers can recognise discrete regions of DNA
M3R (muscarinic receptor) couples with what to produce what second messengers? Beta-2- adrenoreceptor couples with what to produce what second messengers? Majority of GPCRs interact with what?
Gq and PLC–> IP3 or DAG
Gs and AC–> cAMP
PLC or AC
Imbalance of receptors/ chemicals can lead to what?
Chemicals: allergy- increased histamine, Parkinsons= decreased dopamine
Receptors: myasthenia gravis= loss of nicotinic Ach receptors, mastocytosis= increase in C-kit receptor
What is a receptor ligand? What is potency? What is EC50? Agonist?
Anything that acts at a receptor e.g. propranolol
Measure of how well a drug works
Conc that gives half the maximal response
Compound that binds to a receptor and activates it
2 types of normal response curve? Full and partial agonist meaning? Maximal response known as what? How is intrinsic activity calculated?
Linear and sigmoidal (more often used)
Full= 100% response on curve, partial= cannot get maximal response
Emax
Emax of partial agonist/ Emax of full agonist
Antagonist meaning?Competitive vs non-competitive antagonism? Does what to the curves?
Compound that reduces effect of agonist
Compete with agonist to bind receptors- curve shifts to right
Shifts right and down- even more agonist is needed to illicit same response, as it binds near receptor and prevents activation
2 cholinergic receptor types? 2 agonists? Antagonist of muscarinic and nicotinic?
Muscarinic, nicotinic
Muscarine, nicotine
Atropine, curare
Agonist of histamine receptor? Use? Antagonist?
Histamine- contraction of ileum, acid secretion from parietal cells
Mepyramine- reverse contraction of ileum, no effect on acid secretion
What is affinity? What is efficacy? Shown by agonists and antagonists?
How well a ligand binds to the receptor- shown by agonists and antagonists
How well a ligand activates the receptor- only agonists
Less number of receptors at a tissue will result in what? Drug that inactivates a receptor? What equation calculates how many receptors are available?
More drug being required to illicit same effect
BAAM= irreversible B-adrenoceptor antagonist
Furchgott equation
What is a receptor reserve? What is signal amplification? What does it determine?
Hold for a full agonist in a given tissue- can be large/ small, none for partial agonist
Ligand–> receptor–> signalling cascade
How powerful the response will be- this is determined by type of tissue receptor is based in
2 main factors governing drug action? What is allosteric modulation? 2 types? Positive/ negative modulation known as what?
Receptor-related= affinity, efficacy
Tissue-related= receptor number, signal amplification
Binding of an allosteric ligand–> receptor can affect agonists effect on receptor
Affinity- change EC50 value, efficacy- change in Emax
Positive= allosteric, negative= orthosteric
E.g. of allosteric ligand? What is inverse agonism? Tolerance in relation to this? What happens when receptors become desensitised?
Benzodiazepine
Ligand binds to same agonist binding site and has antagonising effect to agonist effect
Reduction in drug effect over time, seen with continuous, repeated high conc of drug over time
Uncoupled- receptor can’t interact with G-protein, receptor= internalised in vesicle of cell, receptor becomes degraded
What does selectivity describe? E.g.s?
The agonist activity
Isoprenaline= non selective B adrenoceptor agonist as it works at both B1 and B2
Salbutamol= selective for B2 although works at B1 too- works better at B2 at lower concs
What is an enzyme inhibitor? 2 types?
Molecule binds to enzyme and decreases normally its activity, prevents substrate–> active site
Irreversible= changes enzymes chemically e.g. via covalent bond formation
Reversible- bind non-covalently, different types depending on whether these bind to enzyme, enzyme-substrate complex, or both
Drugs that target enzymes as drug target? 3 actions of these? Inhibit what enzyme?
NSAIDs e.g. aspirin and ibuprofen, about 50
Analgesic, anti-pyretic (reduces fever,) anti-inflammatory
COX- breaks down arachidonic acid–> prostaglandin H2
Prostaglandin H2 is acted on by specific syntheses to generate what 4 prostanoids? Synthases that produce these are found where? How do NSAIDs prevent PGH2 from forming? How does aspirin differ?
PGD2, PGE2, PGI2, TXA2
PGD2= mast cells, PGE2= macrophages, TXA2= platelets, PGI2= vascular endothelial cells
Prevent arachidonic acid from reaching active site of COX enzyme= competitive inhibition
It binds irreversibly to COX enzyme
COX-1 and COX-2 found where? Aspirin and celecoxib act on what?
COX-1= widely around body, COX-2= inflammation only Aspirin= on both, celecoxib= COX-2 selective
2x e.g. of ACE inhibitors? How do they reduce hypertension? Enalapril and captopril mimic what?
Captopril and enalapril
Prevent ACE (bind to active site) and conversion of angiotensin I to angiotensin II, less vasoconstriction and aldosterone= reduced further
Enalapril (pro-drug)= tripeptides
Captopril= dipeptide
Transporters transport what and most have what activity? E.g. drugs that affect these? PGE2 from chromatin cells bind to what receptors on parietal cells? This reduces what?
Ions and small organic molecules Active- some degree of ATPase activity PPIs- omeprazole, lansoprazole EP3 receptors Activity of H+/ K+ ATPase pump- H+ conc
Histamine from histaminocytes bind to what receptor on parietal cells? This increases what?
H2 receptors
Activity of H+/ K+ ATPase pump- H+ conc increases in gastric lumen
2x e.g. of diuretics? Inhibit what? Furosemide inhibits what resulting in what?
Furosemide, thiazides
Symporters
NKCC2 pump on thick ascending part of loop of Henle- reduced Na+, Cl- and K+ entering medullary interstitium, reduced hyperosmolarity, more water loss in urine
Thiazides inhibit what? 4x e.g. of neuronal uptake inhibitors? Fluoxetine prevents reuptake of what?
Na+, Cl- co-transporter on distal tubule of nephron–> increased water loss
Fluoxetine, imipramine, coacine, tiagabin
Serotonin (SSRI)
Imipramine mostly inhibits reuptake of what? Cocaine? Tiagabin?
Tri-cyclic anti-depressant, noradrenaline (majority) and serotonin
Dopamine
GABA- for panic disorders
3x e.g. of calcium channel blockers used in hypertension? Where does amlodipine block voltage dependent calcium channels?
Amlodipine, verapamil, diltiazem
In cardiac muscle and vascular smooth muscle- prevents influx of Ca2+
What does local anaesthetics like lidocaine and procaine interrupt? They block what? Why pain relief? They can diffuse through what?
Axonal neurotransmission in sensory nerves
Voltage dependent sodium channels- prevents neurones from depolarising
Mucus membrane easily- sometimes can act on muscles too
What does adherence acknowledge? E.g. of lack of adherence?
The importance of patients beliefs, a more patient-centred approach is needed
Not taking medication, taking bigger/ smaller doses than prescribed, more/ less often, stopping without finishing course, modifying treatment to accommodate other activities, continuing behaviours against medical advice
Unintentional reasons for non-adherence?
Practical barriers, difficulty understanding instructions, problems using treatment, inability to pay, forgetting- capacity and resource
Intentional reasons for non-adherence?
Motivational barriers, patients’ beliefs about their health/ condition, beliefs about treatments, personal preferences- perceptual barriers
Ways to tackle non-compliance? Key beliefs in influencing patient evaluations of prescribed medicines can grouped under what 2 categories?
Better patient selection, more education and simplified medical regimens designed to reduce non-compliance
Necessity beliefs- perceptions of personal need for treatment
Concerns- about range of potential adverse consequences
What does patient-centred care encourage?
Focus in consultation on patient as whole person who has individual preferences situated in social context
Shared control of consultation, decisions about interventions or management of health problems with patient
4 pros of good doctor- patient communication?
Better health outcomes, higher adherence to therapeutic regimens in patients, higher patient and clinician satisfaction, decrease in malpractice risk
10 steps in sharing decision making?
Define problem- take in yours and patient’s views, convey that professionals may not have set opinion about best treatment, outline options- consequences of no treatment, provide info in preferred format, check patient’s understanding of options, explore patient’s concerns and expectations, check patient accepts decision sharing process, involve patient in decision-making process to extent patient wishes, review the needs and preferences after patient has had time for further consideration, review decisions over time
Barriers to concordance from health professional and patient point of view?
Patient- may want doctor to tell them what to do, where decisions complex or based on complicated statistical risks
Health professionals- relevant communication skills, time/ resources/ organisational constraints, challenging- patient choice V evident
Key principles in improving concordance?
Improve communication, increase patient involvement, understand patient’s perspective, provide information, assess adherence, review medicines
Ethical considerations with medicines adherence?
Mental capacity e.g. dementia, severe learning disability, brain injury, mental health condition, decision may be detrimental to patient’s wellbeing, potential threat to health of others
What are opiates good for? Bioavailability of morphine if given orally? Lasts how long? Side effects? % population cannot metabolise morphine?
Acute post op/ palliative care- can lead to addiction/ dependency
50% due to liver metabolism
3/4 hours
Resp depression, sedation, nausea, constipation, itching, endocrine effects, immune suppression
10%
Antagonist to morphine? Naturally occurring opioids from opium= what? Simple chemical modifications x3? Synthetic opioids x4?
Naloxone- 400mg/ ml, short half-life so give some IV and some SC so depot will maintain levels
Morphine and codeine poppy
Diamorphine (heroin,) oxycodone, dihydrocodeine (more predictable than codeine)
Pethidine, fentanyl, alfentanil, remifentanil
Synthetic partial agonist opiate? If overdose what happens? SC morphine how long to go around body? IV? How long to reach brain?
Buprenorphine No resp depression 1 hour 1 minute 5 minutes
IV patient controlled analgesia can be self-administered how often? Safe why? Unless?
Every 5 minutes with lockout
Patient will sleep before onset of resp depression, danger if somebody else presses button for delivery
How do opioids work? Designed for use how long? Sustained activation leads to what?
Use G protein coupled receptors- act via 2nd messengers
Inhibit pain transmitter release at spinal cord and midbrain and modulate pain perception in higher centres- euphoria- to change emotional perception of pain
30 minutes
Tolerance and addiction
Opioid receptors? Kappa agonists cause what instead of euphoria? All drugs we use at the moment are what? Located where?
DOP, KOP, MOP and NOP receptors
Mental depression
MOP receptors
Midbrain, spine, GI tract, breathing centre, breathing centre
Potencies of diamorphine, morphine and pethidine? Prolonged use of morphine can do what? Opioid withdrawal beings how soon? Lasts how long? Can give what to provide safer, slower reduction in opioid?
Di= 5mg, morphine= 10mg, pethidine= 100mg Desensitise MOP receptors Within 24 hours Lasts about 72 hours Methadone
Opioids for chronic non-cancer pain leads to what? Codeine is what, so needs what to work?
Loss of effectiveness within weeks, addiction–> manipulative behaviour, difficult to get patient off them
Prodrug, needs to be metabolised by CYP2D6 to work
CYP2D6 activity in caucasian population? Morphine is metabolised to what? Can cause what? Pethidine is metabolised to what?
Decreased in 10-15%, absent in 10%, overactive in 5%- increased risk of resp depression, banned to children and breast feeding mothers= codeine
Morphine 6 glucuronide- more potent than morphine
Resp depression in renal failure
Norpethidine- epileptogenic, cause fits in renal failure
Somatic voluntary NS= what NT? Involuntary autonomic NS what x2 NTs? In autonomic NS, NT for parasympathetic? In sympathetic? Activates what adrenergic receptors?
ACh ACh and noradrenaline (NAd) ACh NAd Alpha and beta
Nicotinic receptors what receptor type? Muscarinic? Effects of Ach in parasympathetic system are mediated by what receptor type? In sympathetic system, Ach mediates release of what NTs?
Ion channel receptors
G-protein coupled receptors
Muscarinic ACh receptors (M1, M2, M3- most common)
Adrenaline and noradrenaline
NT in somatic nervous system? What receptor type mediate response of somatic system at NM junction? Enzyme needed to make ACh? Broken down in synaptic cleft into what by what enzyme?
ACh
Nicotinic receptors
Choline acetyl transferase
Acetylcholinesterase into choline and acetate
How does the botulinum toxin (BOTOX) inhibit ACh release at the NMJ? How does curare/ pancuronium act as a muscle relaxant? How can suxamethonium be used as a muscle relaxant in skeletal muscle paralysis?
Degrades the protein that binds the ACh vesicle to the membrane–> spasticity
Acts as a competitive antagonist- prevents ACh binding at both sites= triple lethal injection in death sentence
Nicotinic receptor agonist w/ 2 ACh molecules- not broken down by AChE, causes persistent depolarisation of motor end plates
What is neostigmine an example of? Useful in what condition? What about pralidoxime? Effects of these depend on what?
Reversible cholinesterase inhibitor- increases ACh in synaptic cleft which isn’t broken down
Myasthenia gravis- antibodies against nAChR–> less receptors, weak skeletal muscle response
Irreversible cholinesterase inhibitor used in organophosphate poisoning- ACh remain indefinitely
Where accumulation is
nAChR= twitching, severe weakness and paralysis
mAChR= salivation, defecation, urination, bradycardia, hypotension
CNS= confusion, loss of reflexes, convulsions, coma
Pilocarpine (muscarinic agonist)= Tx for what? What 2 things can act as short-acting and long-acting bronchodilators? Antagonists at what receptor?
Glaucoma, dry out and simulation of salivary glands- contracts ciliary muscles and constrictor muscles in eye–> miosis and improved filtration of aqueous fluid, lowers intraocular pressure
Ipratropium and tiotropium- muscarinic M3 receptors
What is hyoscine used in? What bladder antagonist can be used to relax the bladder? What 2 GI antagonists can be used to reduced GI motility?
Palliative care and travel sickness- to antagonise PS driven secretions
Oxybutinin- useful in urinary frequency
Mebeverine and scopolamine- in IBS
What are the adverse effects of muscarinic agonists?
Diarrhoea, urination, miosis, bradycardia, emesis, lacrimation, salivation/ sweating= DUMBELS
Hexamethonium blocks what of the autonomic NS? These blocks cause what? Used as the 1st what?
Both PS and sympathetic divisions
PS–> secretions reduced, constipation, urinary retention, blurred vision
Sympathetic= marker hypotension
Hypertensive drug
Scopolamine is used for what? ACh stimulates the reuptake of what NT? What drug blocks this reuptake and increases the amount of dopamine at the cleft?
Motion sickness treatment
Dopamine
Benzatropine
There is a lack of what in Alzheimers? What drug can act to inhibit acetylcholinesterase?
Cholinergic neurones and ACh reduction
Donepezil
What is the precursor to adrenaline and noradrenaline? Stimulation of PS NS leads to what effects?
Dopamine
Rest and digest, constricts pupils, stimulates tears, salivation, lowers HR, reduces respiration, constricts blood vessels, stimulates digestion, contracts bladder
Stimulation of sympathetic NS leads to what?
Fight/ flight, dilates pupil, inhibits tears, inhibits salivation, activates sweat glands, increases HR, increases respiration, inhibits digestion, release of adrenaline, relaxes bladder, ejaculation in males
Flow of adrenaline synthesis? What 2 enzymes inactivate Nad release by metabolising it, reducing its stimulant effect? Also metabolises what?
Tyrosine–> DOPA—> dopamine—> noradrenaline—> adrenaline
MAO and COMT
Adrenaline and dopamine
Classes of alpha and beta adrenoceptors? All of these are what receptor type?
Alpha= alpha-1 and alpha-2, beta= beta-1, beta-2 and beta-3
G-coupled protein receptors
Alpha-1 adrenoceptors are coupled with what? Alpha-2? Effects of alpha-1 and alpha-2 adrenoceptors?
Gq protein and phospholipase C
Gi, inhibits adenyl cyclase
Alpha-1= vasoconstriction, pupil dilation, bladder contraction
Alpha-2= presynaptic inhibition of noradrenaline i.e. when blood sugar is low, in pancreas reduces NAd, reducing insulin from pancreas
Beta-1,2 and 3 all coupled with what? Effects of beta-1, 2 and 3 beta-adrenoceptors?
Gs protein and adenyl cyclase
Beta-1=increased force of heart contraction, HR, electrical conduction in heart, renin release from kidney, BP
Beta-2= bronchodilator, vasodilation, reduced GI motility
Beta-3= increased lipolysis, relaxation of bladder
Adrenaline is a what? Uses? Targets? Effects?
Non-selective agonist- works at any alpha or beta adrenoceptor Anaphylaxis- reduced BP and increased bronchoconstriction cardiac arrest, acute hypotension Blood vessels (alpha-1), heart (beta-1,) bronchial smooth muscle (beta-2) Vasoconstriction, positive inotropic effect, bronchodilation
2x selective adrenergic agonist at alpha-1 receptors? At alpha-2 receptor? At beta-1? Beta-2? Beta-3?
Phenylephrine and oxymetazoline--> vasoconstriction and nasal congestant Clonidine- anti-hypertensive Dobutamine- positive inotropic effect Salbutamol- bronchodilation Mirabegron- bladder relaxation
How do amphetamines and cocaine work? MAO and COMT inhibition useful for treating what?
Inhibit the noradrenaline transport on pre-synaptic neurone–> catecholamine build-up
Parkinson’s and depression
Doxazosin is an example of what? Tamsulosin does what? Yohimbine example of what? Beta-1 antagonists used to treat what?
Alpha-1 antagonist= anti-hypertensive
Relaxes bladder neck- aids in urination
Alpha-2 antagonist- increase in catecholamines
Hypertension, angina and arrhythmia
Propanolol is a what? E.g. x4 of beta-1 selective? Carvedilol is a what? E.g.x2 of partial agonists of beta-adrenergic receptors? These do what? Known as what?
Non-selective B-adrenoceptor antagonist- all B receptors
Atenolol, metoprolol, bisoprolol, betaxolol
Non-selective beta and alpha-1 antagonist
Penbutolol and acebutolol- stimulate beta-adrenergic receptors as well as acting like antagonists too
Intrinsic sympathomimetic activity (ISA)
E.g. x2 that can inhibit the propagation of action potentials across a membrane? Known as what? Useful for treating what?
Propanolol and betaxolol
Membrane stabilising activity (MSA)
Arrhythmias
What is a adverse drug reaction? 5 types?
Response to a drug which is noxious and unintended
A= augmented, B= bizarre, C= chronic, D= delayed, E= end of use
Type A ADR and examples x3? Those with what at higher risk of ADR?
Commonest, extension of clinical effect, predictable, dose related, self-limiting e.g. diuretic–> dehydration, anticoagulant–> bleeding, hypertension–> hypotension
Renal/ hepatic impairment- elimination difficulties, high blood plasma levels of drug for longer
Elderly= decreased GFR and hepatic impairment
Type B ADR and e.g.? Greater risk who? Can be seen where?
Unexpected, unrelated to dosage and not expected, unpredictable, mostly immunological mechanisms, hypersensitivity e.g. heparin—> hair loss
History of allergy, asthmatics, family history
In drugs inhibiting metabolic pathways, genetically linked
Type C ADR and e.g.? Type D and e.g.?
After long term therapy, may not be obvious with new medicines e.g. steroids predispose to hypoglycaemia–> may diabetes
After long period of time after treatment- many years e.g. teratogenesis after thalidomide, neoplasia
Type E ADR? Factors susceptible to ADR?
Relatively long term use (days/ weeks,) withdrawal reactions, serious complication of stopping related to clinical effect
Age, gender, pregnancy, disease, drug interactions, diet or alcohol intake changes, genetics
What is type 1 hypersensitivity? Type 2? Type 3? Type 4?
IgE-mediated drug hypersensitivity- anaphylaxis
IgG-mediated cytotoxicity- some can cause renal failure through this type
Immune-complex deposition- reacts with antibiotics
T-cell mediated, usually substance containing metals
Type 1 hypersensitivity involves what? What are mast cells, many found where, lot of mast cell activity where?
Prior exposure to antigen, virgin B lymphocyte to activation to IgE producing plasma cells–> mast cells expressed as cell surface receptors
In skin, sub mucosal, around blood vessels, dormant indefinitely, many found in bronchial mucosa, see lot of activity beneath skin, around lungs and blood vessels
Mast cell degranulation releases what? Non-immune anaphylaxis previously known as what?
Cross linking of IgE receptors–> histamine, thromboxjnes, prostaglandins, tumour necrosis factor (TNF)= acute inflammatory mediators
Anaphylactoid reactions- not caused by IgE, due to direct mast cell degranulation, some drugs recognised to cause this, no prior exposure
Main features of anaphylaxis? Alternative presentation?
Exposure to drug, immediate rapid onset, rash with characteristic blotches, swelling of lips, face, oedema, central cyanosis, wheeze, hypotension, cardiac arrest
Cardioresp arrest, no skin changes
Management of anaphylaxis? Adrenaline effect?
Basic life support; A, B, C
Stop drug if infusion, adrenaline 1mg (10mls of 1:10,000 (IV) 1ml IV increments)- if CA, may need cardiac massage to get drugs circulating
IV anti histamine (chlorphenamine 10mg)
IV hydrocortisone (100 to 200mg)- unlikely to cause harm in excess so can’t really give too much
Vasoconstriction, bronchodilation and increased CO
Risk factors for drug hypersensitivity?
Medicine factors- protein/ polysaccharide base macromolecules e.g. penicillin
Mono-clonal antibodies (proteins) can cause reactions
Host factors- more common in females, immunosuppression
Genetic factors- certain HLA factors
What to do if ADR expected? Identify markers for type A and B ADRs?
Elicit full medication history and previous reactions
Check useful resources to find if ADR is described e.g. BNF, eMC, MHRA
A: serum concentration- plasma monitoring
B: tryptase, released from only mast cells, urine methylhistamine- breakdown of histamine
Managing Type A and B ADRs?
A: may respond to dose-reduction or temporary withdrawal, severe may require active treatment
B: should usually withdraw medicine immediately, give supportive treatment if reaction severe
Main method of surveillance of ADRs? Should report what?
MHRA Yellow-card scheme- complete it online, post/ phone
All ADRs for new meds, all ADRs in children, all serious reactions, even if well-documented to include: fatal, life threatening, disabling, incapacitation or which result in prolong hospitalisation
What is an allergy? What is atopy?
Abnormal response to harmless foreign material (allergens)
Tendency to develop allergies, hereditary predisposition to development of immediate hypersensitivity reactions against common environmental antigens
6x e.g. of drugs used in IV drug therapy? Why are IV infusions used?
Insulin, heparin, antibiotics, furosemide, anti-arrhythmic, sedation anaesthesia
Enables steady state plasma levels to be maintained for as long as possible, enables highly accurate drug delivery, useful for drugs ineffective administered by other routes/ cannot absorb oral medication, quickest admin route, guarantees 100% bioavailability
Pro and con of oral administration?
Much less accurate drug delivery–> uncertainty of effectiveness of treatment
Excellent patient compliance with one tablet a day
Pros and cons of IV infusion?
Requires constant monitoring of latency of IV access, replenishing of drug delivery and observation of response to therapy
Has potential for serious calculation errors
Limited by number of places cannula can be inserted
IV regimes lack what? Units are what? Drug dosage is based on what? Problematic with what? Monitoring necessary to look at what?
Standardisation of prescription
Mg/ hour
Body weight- extreme body weights
Therapeutic response
High volume of distribution of a drug means what? Issue with adjusting infusion rates of these? What is needed to speed up saturation of all the components?
There will be a small fraction in the plasma, so it will take a long time to reach a steady state
It takes ages to change the plasma concentration
‘Loading’ bolus dose
What does steady state mean? Increasing infusion rate aims to do what? If elimination becomes saturated, what will this lead to?
Infusion dosage= rate of elimination from plasma
The accumulation of the drug and thus toxicity
4 features of an ideal drug for infusions?
One with small volume of distribution- easy to reach steady state, so plasma conc is responsive to dose rate
Broken down by tissue/ plasma enzymes irrespective of liver and renal function
One with obvious and predictable dose to response relationship
One with low risk of toxicity and easy to determine conc of it in plasma
Insulin is infused with what for managing a diabetic who is nil by mouth? Why is there a danger of hypoglycaemia if insulin is not given alongside dextrose? What does vancomycin infusion require?
10% dextrose
Plasma glucose can change rapidly
Plasma level monitoring of peak and trough level after 3 doses
Amiodarone infusion has problem of what when infusion is turned off? Is high volume of distribution drug and thus often steady state is not achieved after how many hours of IV infusion? Heparin infusion for what, works when?
Returning arrhythmia
48 hours
For emergency anticoagulation if at high risk of thrombosis, chemical reaction works in minutes
Noradrenaline used as what, given for treatment of what? Continuous infusion of GnRH results in what? Pulsatile is what? What occurs with many agonist drug infusions? What could avoid this?
Alpha-1 agonist as a vasoconstrictor- for septic shock
Contraceptive effect
Physiological fertility treatment
Desensitisation- pulsatile delivery
Pulsatile IV gentamicin results in what? Patient controlled morphine analgesia only requires what fraction of normal IV dose if given as intermittent IM injections? Why is this beneficial?
Higher peak level than steady infusion and thus higher bactericidal activity
1/3
Less resp depression than with IV infusion
What is homeopathy and advantage? E.g. x4 of medical medical herbalism from plants? Pro and con?
To treat like with like, quite possible there is a placebo effect
Unlikely to be any drug interactions
Digitalis from foxglove plant- heart failure treatment
Morphine from poppy- analgesic
Atropine- from deadly nightshade- scarlet fever treatment
Vincristine from periwinkle- cancer treatment
Can be medically effective, industry= unregulated e.g. heavy metals found in asian herbal products
E.g. x4 drugs created by chance/ rational drug design? What are alkaloids? Most ACE-inhibitors are what? Penicillin developed using what? Led to what?
Penicillin, sildenafil
Propanolol, ritonavir
Nitrogen containing rings that attract protons
Pro-drugs- need to be metabolised into active drug
Fermentation—> discovery of other antibiotics such as streptomycin
3x e.g. drugs developed via fermentation approach? What factor may influence drug action? Biological systems use what amino acid type?
Lovastatin(statin,) cyclosporine (immunosuppressant,) ivermectin (broad spectrum antibiotic)
Chirality e.g. salbutamol= chiral centre
L-amino acids (R form)
Propanolol was developed as a what? Cimetidine developed as a what? Used in treatment of what?
Antagonist to counter the agonist noradrenaline- is a B-antagonist used in treatment of hypertension
Antagonist to counter the agonist histamine
H2- antagonist used to treat peptic ulcers
Insulin extracted first from what? e.g. x3 each of fast-acting and long-acting insulin analogues?
Beef/ pork pancreas
Lispro, aspart, glulisine
Degludec, detemir, Glargine
6x recombinant proteins in clinical use? Therapeutic antibodies based on what? MAb produced how?
Insulin, erythropoietin, growth hormone, interleukin 2, gamma interferon, interleukin 1 receptor antagonist
mAb technology
Mouse immunised against antigen of interest, B cells isolated to check producing ABs, spleen removed
B cells in spleen removed and cultured along with myeloma tumour cells, solution added to fuse B cells with tumour cells–> hybridomas, cloned and undergo clonal expansion, MAbs extracted and then used for clinical purposes
1st generation MAbs? 2nd generation? Humanised antibodies? Why MAbs and humanised mABs recognised same target e.g. TNF?
Mouse derived and thus tended to illicit immune response against themselves since immune system recognised antibodies as foreign- poor half-life
Chimeric- mix of human and mouse antibody, mouse AB present= can illicit immune response
Humanised= 3 hypervariable regions less likely to illicit immune response
Due to similarities in hypervariable regions
What is gene therapy?
Delivery of nucleic acid polymer to cell, DNA is delivered using viral vector, therapeutic gene administered to treat effects of mutated gene
Suppresses mutated gene gene expression
What is combinatorial chemistry? Important sources of natural products? Con?
generation of leads: biochemical modification of natural products e.g. penicillin, cyclosporine, quinine, morphine
Tropical rain forest and sea
Chemical modifications of natural product may be very difficult
What is combinatorial biosynthesis? How many compounds can high throughout screening (HTS) screen? Looks at what? Rapid way to identify what? HTS cannot establish what? Path from lead to drug is what?
Large enzyme complexes generate natural products, then manipulate biosynthetic machinery to generate structural analogues
50,000 a day, roughly 2.5 million a year
Biological activity of compounds
Computers collate and retrieve data and analyse whether any compound has clinical efficacy
‘Hits’
Bioavailability, pharmokinetics, toxicology- tested for using traditional methods
Very long, expensive and has high attrition rate
What is pain? 3 features of positive role? 3 physiological effects?
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
Warning of tissue damage, immobilisation for healing, protection of the species: establishment of memory
Increased HR, BP and RR
Acute pain lasts how long, results from what? What are nociceptors?
Non-surgical cause (most common,) post op pain, generally less than a week, from activation of sensory nerve fibres called nociceptors
Nerve endings of peripheral nervous system, myelinated A delta fibres, unmyelinated C afferent fibres, in most body tissue except brain
E.g. x2 of non-cancer chronic pain? 7 steps of pain pathway? excitatory NT used?
Visceral and musculoskeletal pain
Noxious stimulus, nociceptors, spinal cord (ascending pathway,) spinal cord modulation, thalamus, cortical areas, somatosensory cortex and prefrontal cortex, pain experience and memory
Glutamate
Breakdown of lipids leads to formation of what? Under action of what? Converted to prostaglandins under action of what? Prostaglandins are irritants to what? Products of arachidonic acid do what?
Arachidonic acid under action of enzyme phospholipase A2
COX enzyme
Nerve fibres and stimulate pain
Act directly on nociceptors and lower their threshold to thermal stimuli–> burning sensation at room temp
Pain from C fibres? Myelinated? A delta fibres? There is a balance of activity between small (A delta and C fibres) and what? Interneurons of the substantia gelatinosa regulate the input in what?
Unmyelinated, diffuse dull intense pain
Small and myelinated, conduct localised sharp sensation
Large (A beta fibres)
Lamina V (dorsal horn of spinal cord)
If A beta fibres are not stimulated by nociceptive stimulus, then what happens? What if they are stimulated? What will therefore generate analgesia?
Pain signal goes through brain and perceived
Pain signal is halted and does not reach the brain and is thus not perceived
Low intensity stimulation of skin/ peripheral nerves or vibration in order to stimulate the A beta fibres
4 applications to pain? 2 things play role in endogenous pain system? They inhibit what? Changing what means less pains transmitted?
Rubbing site of injury, application of heat, TENS- trans cutaneous nerve stimulation of A beta fibres, spinal cord stimulation
Peri aqueductal grey and locus cerulus
Firing of the dorsal horn neutron that response to noxious stimulus (gate control theory)
The levels of neurotransmitters at the level of synapses
Peri aqueductal grey contains high conc of what? When can this pathway be activated? Results in what and projects where? Activation of opioid receptors results in what?
Opioid receptors and endogenous opioids
Under situations of extreme stress
Modulation of afferent noxious transmission, projects to dorsal horn
Reduction of pre-synaptic neuronal sensitivity, reduction of substance P release and reduced pain sensation, less impulses up 1st, 2nd and 3rd order neurones to somatosensory cortex
3 endogenous opioid peptides? Opioids such as what mimic this effect by binding to opioid receptors in periaqueductal grey, conferring profound analgesia?
Enkephalin, dynorphine, beta endorphine: effect similar to morphine
Morphine, methadone, codeine and oxycodone
Basis of pharmacological treatment of some pain? Local anaesthetics are what?
Reducing excitatory NTs (glutamate) and excitation of nerve- basis for anti epileptics
Na+ channel blockers
Enhancing inhibitory NTs- GABA= main inhibitory, noradrenaline and serotonin= basis for anti-depressants
What are released in the presence of pain? Practical utilities? How do prostaglandins affect nociceptors? What utilises this? How do local anaesthetics work?
Endorphines
Acupuncture- bearable pain, placebo, psychological modulation of pain
Act directly and reduced their threshold, so normal stimuli can activate them resulting in sensation of pain
NSAIDs and possibly paracetamol
Block conduction of nerve by blocking Na+ channels- prevents depolarisation of nerve and propagation of AP
What is chronic pain? Effects on patient and their family? Principles of treatment of chronic pain?
Ongoing pain greater than 3-6 months
Beyond usual course of acute disease, after healing/ cure take place, at intervals for months/ years, persisting stimulation in areas of ongoing tissue damage
Physical: immobility, emotional: distress, social: little social interaction= isolation, economical= job issues, day to day activity= severely affected
Improve pain perception, improve function/ mobility, improve sleep, improve emotional and psychological consequences of pain, improve quality of life
What is needed for a prescription? Included on a prescription?
Diagnosis, drug treatment, indications and contraindications, peculiar properties either diagnosis or drugs: does it require plasma monitoring? is there a risk of drug interaction?
Patient name, dose, route, freq, duration, total number of tablets, drug name, date and signature
Error potential in what 4 things?
Home: drug history and pharmacy printout
Hospital admission: in patient prescription chart
In patient: MD prescribing
Discharge from hospital: take home medication or not and discharge summary to GP
5 potential sources of error?
Number of different times the same info is translated or transposed
Inadequate information of admission
Duplication; paper, different teams
Clerical/ legibility/ administration errors
Emergency situations
Ward pharmacists check prescriptions how often? Tazocin and augmentin contain what? Try to avoid what with oramorph? Specify clearly between IV and what?
Daily
Penicillin- check for penicillin allergy
Underprescription
IV and intrathecal- can lead to spinal cord damage
Can get withdrawal reactions if stopping what long-term drugs?Vast majority of drugs should be continued unless what?
Analgesics, anti-hypertensives and anti-depressants
There is a specific reasons to do with the presenting complaint
Nil by mouth policy before surgery is how long? Due to fear of what? Can safely have what though? Drugs should be discontinued before surgery?
2 hours- aspiration under anaesthesia
Small drop of water for medications prior to surgery
ACE inhibitors, Losartan, warfarin- should be bridged to heparin, (easier to manage dosage since injected), diabetes drugs- detailed guidance proforma exists
Legal obligation for any doctor that suspects case of notifiable disease to inform who? 3 diseases that aren’t notifiable?
Proper Office of Local authority
HIV, bird flu or variant Creutzfeldt- Jakob (vCJD)
Notifiable diseases that are scary/ nasty? Diseases that are vaccine preventable? Diseases that need specific control measures?
Anthrax, rabies, cholera, leprosy, malaria
Acute poliomyelitis, measles, mumps, rubella
Acute infectious hepatitis, scarlet fever, tuberculosis
Why notify about notifiable diseases?
Detection of any changes in disease: outbreak detection, early warning, forecasting, extent and severity of disease, risk factors
Allows the development of interventions targeted at vulnerable groups
How is community protected from notifiable diseases?
Investigate to see who might have been exposed to the disease: contact tracing, partner notification
Identify and protect vulnerable persons: chemoprophylaxis, immunisation, isolation
Exclude high risk persons from high risk setting: educate, inform and raise awareness
Clinical indications related to allergy? What is an allergy? What is atopy?
Epithelial- eczema, itching, reddening Excessive mucus production Airway construction Abdominal bloating, vomiting, diarrhoea Anaphylaxis
Abnormal response to harmless foreign material
Inherited tendency for overproduction of IgE antibodies to common environmental antigens
Low affinity IgE receptor expressing cells? They function to do what? x3
B cells, T cells, monocytes, platelets and neutrophils
Regulate IgE synthesis, trigger cytokine release by monocytes,
antigen presentation by cells
High affinity IgE receptor expressing cells? Involved in host defence against what? Eosinophils express a different range of granule contents to what? Main effector cells for IgE-mediated immunity? Characterised by requirement for what? Immature mast cells do what that mature don’t? Maturation occurs where?
Eosinophils, mast cells and basophils Mast cells and basophils Mast cells C-kit protein Circulate Specific tissue environments
E.g. of preformed compounds? E.g.s/ functions of each?
Histamine, chemotactic factors, proteases, prostaglandin D2, platelet activating factor (PAF)
Arteriolar dilation, capillary leakage, induces bronchoconstriction
Chemotactic factors- some cytokines e.g. IL-4
Typically lead to eosinophil attraction and activation
Tryptase, chymase
Potent inducer of smooth muscle constriction
Increases platelet aggregation and degranulation, increases vascular permeability, activates neutrophil secretion
2x e.g. of indirect activators (via IgE)?
Allergens- latex, wasp/ bee venoms, foods, drugs, pollens and house dust mite faeces
Prior sensitisation is required generally through mucosal surface
Bacterial/ viral antigens- protein L of pneumococcus Magnus, protein A of S.aureus
gp120 of HIV-1
Phagocytosis
Direct activators of allergy?
Cold/ mechanical deformation i.e. asthma
Aspirin, tartrazine, preservatives, nitric oxide
Complement products- C3a and C5a
Other cells involved in allergy?
Lymphocytes- Th2, dendritic cells, neurons, other non-immune cells: fibroblasts, epithelia, smooth muscle
What 4 things makes an allergen?
Particulate delivery of antigens, presence of weak PAMPs resulting in weak innate immunity activation but not adaptive immunity since then will develop memory
Nasal/ skin delivery, low doses
Anaphylaxis occurs in how long? Features of?
Minutes or hours, IgE or direct activation, elevated serum tryptase and histamine
Vasodilation, increased vascular permeability, lowered BP, bronchia smooth muscle contractions, mucus production, rash, swelling, stomach pain and vomiting
3 methods of allergy treatments- desensitisation?
Immunotherapy, preventing mast cell activation, reducing mast cell products
How does immunotherapy work?
Increasing dose of antigen via sub-lingual or subcutaneous, has limited use, only really in atopic eczema, of no use in asthma, usually only really serious conditions
How would mast cell prevention work? How would mast cell products be reduced?
Beta 2 agonists- increased cyclic AMP
Glucocorticoids- inhibit gene transcription but some long term effects
Histamine receptor antagonists, prostaglandin antagonists e.g. leukotriene results in inhibition of activation of TH2 cells
Tryptase inhibitors- prevent away smooth muscle activation
Features of type 1 Gell and Coombs reactions? Type 2? Type 3? Type 4?
Acute anaphylaxis, hay fever, immediate and acute
IgG bounds to cell surface antigens/ IgM, transfusion reactions, autoimmune disease, fairly quick
Immune complexes, activation of complement/ IgG, SLE, post-streptococcal GN
T cell mediated delayed type hypersensitivity (DTH), TB, contact dermatitis
E.g. of type 1 reactions? What cells play major role in complex allergic conditions such as asthma by activating and recruiting IgE antibody-producing B cells, mast cells and eosinophils? Cytokines released? Can diagnose atopy with what test?
Hay fever, asthma, eczema
T lymphocytes- TH2 cells
IL-4, IL-13
Skin prick test
T cells trigger mast cells to secrete what? If they secrete large amounts and enter circulation, what systemic symptoms may result?
Inflammatory mediators- histamine and chemokines
Severe hypotension, vasodilation and bronchoconstriction
Type 2 reactions leads to what? E.g. of this? How does this happen?
Tissue injury, altered receptor function
Haemolytic disease of newborn, mother= rhesus negative blood, baby= rhesus positive, antibodies produced, first baby= unaffected, mother= sensitised to rhesus positive blood
2nd baby= antibodies produced to destroy babies RBCs–> anaemia, jaundice, can cross placenta= rhesus disease
What antibody binds to soluble antigens to form circulatory complexes in type 3 reactions? Little lumps of target and antibody are deposited where? Activates what? Symptoms of farmers lung? Other similar e.g.?
IgG
In skin, lung, kidney etc.
Immune response and local inflammation resulting in tissue damage
Mouldy hay inhaled–> fever, cough, flu-like illness, breathlessness, crackles= local inflammatory response
Malt-workers lung, mushroom workers lung, pigeon fanciers lung
Acute post streptococcal glomerulonephritis? Results in what?
Occurs roughly 10-12 days after streptococcal infection of throats or skin and results in deposition of immune complexes of IgG and C3 in glomerular basement membrane
Streptococcal antigens bind to glomerular basement membrane thereby localising antibody to site and triggering an immune response
Type 4 reactions are independent of what? Mediated by what 2 cells? Increased cytokines by Th cells activate what? Takes how long? Seen in what diseases? E.g. from poison ivy?
Antibodies
Th cells and macrophages
Macrophages to secrete their potent mediators
Several days= delayed hypersensitivity
Granulomatous disease- such as sarcoidosis
Contact dermatitis
