ICS - Pharmacology Flashcards
What is synergy?
Interaction of drugs such that the total effect is greater than the sum of the individual effects
What is antagonism?
An antagonist is a substance that acts against and blocks an action (2 drugs opposed to each other)
What is summation?
Different drugs used together to have the same effect as a single drug would
What is potentiation?
Enhancement of one drug by another so that the combined effect is greater than the sum of each one alone
Define pharmacodynamics
The effect the drug has on the human body
Define pharmacokinetics
What the body does with the drug (the disposition of a compound within an organism)
What are the 4 pharmacokinetic mechanisms within the body?
Absorption, distribution, metabolism, excretion (ADME)
How can absorption reduce drug effectivity?
Motility - if the gut has slowed digestion, the drugs won’t work as well
Acidity - pH and pHa interactions
Complex formation
What is the significance of distribution in regards to drug interaction?
Drugs can go into the proteins, other tissues or to the effect site
If you give 2 highly protein bound drugs, they will make each other stronger and increase their effect, so you always have to Make sure what drugs the patient already takes before giving new drugs
What effect does the metabolism have on drug interaction?
Inhibition - drug A blocks metabolism of drug B, leaving more free drug B in the plasma so it has an increased effect
Induction - Drug C induced CYP450 isoenzyme leading to increased metabolism of drug D so it has a decreased effect
What effect does excretion have on drug interaction?
Weak bases - cleared faster if urine acidic
Weak acids - cleared faster if urine alkali
Name 2 examples of drug interactions to be aware of
Warfarin (lots of interactions)
Acute Kidney Injury - NSAIDs and ACEi
Define drug
A medicine or other substance which has physiological effect when ingested or otherwise introduced into the body
What proteins in the body are targets for drugs?
Receptors, enzymes, transporters, ion channels
Give an example of a condition caused by imbalance of chemicals
Parkinson’s = reduced dopamine
Give an example of a condition caused by imbalance of receptors
Myasthenia Gravis = loss of Ach receptors
What are the two types of cholinergic receptor?
Nicotinic and Muscarinic
Define signal transduction
A basic process involving the conversion of a signal from outside the cell to a functional change within the cell
Define signal amplification
To increase the strength of a signal
What makes an inhibitor reversible?
It binds non-covalently
What changes occur in RAAS when ACE is inhibited?
Angiotensin II production is reduced, causing a reduction in blood pressure
Define active transport
Ions move from a lower concentration to a higher concentration
What are the 3 main types of protein ports in cell membranes?
Uniporters - use energy from ATP to pull molecules in
Sympoters - Use the movement in of one molecule to pull in another against a concentration gradient
Antiporters - one substance moves against its gradient, using energy from the second substance moving down its gradient
Give 3 examples of how we develop drugs
Medicines from plants
Organic molecules
Stereoisomers
Immunotherapy antibodies
Define adherence
The extent to which the patient’s actions match agreed recommendations
Give 4 impacts of good patient-doctor communication
Better heath outcomes
Higher adherence to therapeutic regimens in patients
Higher patient and clinical satisfaction
Decrease in malpractice risk
Give 2 examples of how a drug might pass across a membrane
Passive diffusion through the lipid layer
Carrier mediated processes
What obstacles must drugs overcome before they reach the systemic circulation?
Drug structure - must be lipid soluble to be absorbed from the gut
Drug formulation - tablet must dissolve
Gastric emptying - rate of emptying determines how soon a drug is delivered
First pass metabolism - drugs must pass metabolic barriers (intestinal lumen, liver, lungs)
What is a limitation of inhalation absorption?
Risks of toxicity to alveoli
How are drugs eliminated from the body?
Through the metabolism or excretion
Describe the 2 phases of drug metabolism
Phase 1 - transformation of the drug to a more polar metabolite
Phase 2 - formation of a covalent bond between drug and an endogenous substrate
How are drugs/metabolites excreted?
Fluids - urine excretion: total excretion = glomerular filtration + tubular secretion - reabsorption
Solids - faeces
Gases - expired air (volatiles)
Define first order kinetics
Change in concentration at any time is proportional to the concentration
Define zero order kinetics
The change in concentration per time is a fixed amount of drug per time, independent of concentration
Define half life
The time takes for a concentration to reduce by one half
Define bioavailability (F)
Fraction of the administered drug that reaches the systemic circulation unaltered
What bioavailability do IV drugs have?
F = 1 has 100% of drug reaches circulation
What bioavailability do oral drugs have?
Oral drugs may have F<1 if they are incompletely absorbed or undergo first pass metabolism
Define tolerance
Down regulation of the receptors with prolonged use. Need higher doses to achieve the same effect
Name 3 side effects of opioids
Nausea and vomiting
Immune suppression
Respiratory depression
What is cholinergic and adrenergic pharmacology responsible for?
Control of blood pressure Control of heart rate Anaesthetic agents Regulation of airway tone Control of GI function
Where are each of the 5 muscarinic receptors located?
M1 - brain
M2 - heart
M3 - glandular and smooth muscle
M4/5 - CNS
Name 4 side effects of anticholinergics
Brain - worsen memory, cause confusion
Peripherally - constipation, worsening of glaucoma
What is the effect of alpha 1 activators?
Raise blood pressure - causing vasoconstriction
What is the effect of alpha 2 activators?
Lower blood pressure
What are the uses of beta agonists?
Beta 1 - activation will increase HR and chronotropic effects
Beta 2 - activation is life saving in asthma
Beta 3 - agonists can reduce over-active bladder symptoms
What is the effect of beta blockers?
Lower blood pressure, reduce cardiac work, treat arrhythmias
When would beta blockers be used?
Angina, MI prevention, high BP, heart failure
What are some side effects of beta blockers?
Tiredness, bronchoconstriction, bradycardia, heart failure
Define allergy
An abnormal response to harmless foreign material
What cells are involved in the pathogenesis of allergies?
Mast, eosinophils, lymphocytes, dendritic, smooth muscle, fibroblasts, epithelia
Name 3 examples of allergic disease
Anaphylaxis, allergic asthma, food allergies, contact dermatitis
Define adverse drug reactions
Unwanted or harmful reactions following the administration of drugs or combination fo drugs under normal conditions of use and is suspected to be related to the drug
What are the causes for ADRs?
Pharmaceutical variation, receptor abnormality, drug-drug interactions
Name 3 common ADRs
Confusion, diarrhoea, constipation, hypotension
What 4 pieces of critical information are included on a yellow card?
Suspected drug, suspect reaction, patient details, reporter details
Describe a type 1 hypersensitivity reaction
IgE mediated
Acute anaphylaxis after prior exposure to the antigen
IgE becomes attached to mast cells or leukocytes, expressed as cell surface receptors
Describe a type 2 hypersensitivity reaction
IgG mediated cytotoxicity
Body treats it as a foreign protein and forms antibodies. Antibodies combine with the antigen and complement activation damages the cells
Describe a type 3 hypersensitivity reaction
Immune complex deposition
Small blood vessels are damaged or blocked
Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process
Describe a type 4 hypersensitivity reaction
T cell mediated
Lymphocyte mediated
Antigen specific receptors develop on T-lymphocytes
Define anaphylaxis
An acute allergic reaction to an antigen to which the body has become hypersensitive
What are the main features of anaphylaxis?
Exposure to drug, immediate rapid onset rash
Swelling of lips, face, oedema, central cyanosis
Hypotension
Cardiac arrest
What is the difference between tolerance and desensitisation?
Tolerance - reduction in drug effect over time (continuously repeated high conc)
Desensitisation - receptors become degraded/ uncoupled/ internalised
What class of drug is Candesartan?
Angiotensin II Receptor Blocker
In what respiratory condition are beta blockers contraindicated and why?
Asthma - beta blockers cause bronchoconstriction
What do NSAIDs inhibit and what is the result?
Cyclo-oxygenase enzyme, prevents the conversion of arachidonic acid to prostaglandin H2
What are the different types of ADR?
A - augmented B - bizarre e.g. allergy C - chronic use D - delayed e.g. malignancy after immunosuppression E - end of treatment - withdrawal
What is the steady state?
Constant drug conc in blood/site of effect for therapeutic use
What is the loading dose?
High initial dose to shorten time to reach steady state
What is druggability?
The ability of a protein target to bind to small molecules of high affinity
What is affinity?
How well a ligand binds to a receptor
What is efficacy?
How well a ligand stimulates a receptor
What is the effect is stimulating adrenergic alpha 1 receptors?
Smooth muscle contraction
What is the effect is stimulating adrenergic beta 1 receptors?
Increased chronotropic/ inotropic effects
What is the effect is stimulating adrenergic beta 2 receptors?
Smooth muscle relaxation
What is the effect is stimulating adrenergic beta 3 receptors?
Increase lipolysis and relaxes detrusor muscle
