Pharmacology

Question	Answer
What is the major difference between full and partial agonists?	The maximal response decreases with partial agonists.
What happens to competitive antagonists when the agonist concentration is increased?	The competitive antagonists can be displaced from receptors
List some schedule 8 drugs	Morphine, ketamine, oxycontin, fentanyl, methylamphetamine
How might the carcinogenic potential for a new drug first be tested?	Chronic dosing in a rodent over the animal’s lifespan, with organ pathology assessed for tumour development
What is therapeutic index?	The plasma drug concentration range or the dose that provides efficacy without toxicity.
How is therapeutic index measured?	LD50 = lethal to 50% of the population ED50 = effective in 50% of the population TI = TD50/ED50
List common parenteral routes of drug administration.	IV, IM, subcut, rectal, patch, inhalant, under tongue
What is steady-state concentration?	The concentration of a drug or chemical in a body fluid – usually plasma – at the time a “steady state” has been achieved, and rates of drug administration and drug elimination are equal.
Describe pharmacotherapeutic applications w/ eg	Classified according to the condition (disease) to be treated. eg. anticancer (or anti- inflammatory, antiviral, anticonvulsant)
Describe pharmacological actions w/ eg	Classified according to primary pharmacological action (or- how the drug exerts its effect on the body) eg. β(beta) blockers
Describe chemical structure w/ eg	Classified according to structurally-related compounds possessing similar pharmacological actions. eg. steroids (or benzodiazepines, barbiturates, tricyclics)
Briefly describe FIVE support systems that are designed to allow safe administration of controlled drugs.	Controlled drugs - possession, storage, supply, prescribing and administration restricted to reduce abuse, misuse and dependence Monitor pt before and after administration Know the effects of controlled drugs and their reversal agents Follow the 8 rights of drug administration Refer to institution protocols when administering controlled drug
Describe the four stages of clinical drug development	I. Assessment of safety and drug pharmacokinetics in a small number of healthy adults II. Assessment of drug effectiveness and dosing in a moderate number of patients III. Large randomised controlled trials in patients across several different centres IV. Monitoring of drug effectiveness and any adverse health outcomes after regulatory approval
What is ARTG Register Classification?	Australian Register of Therapeutic Goods - drugs supplied in Australia must be entered on this register. Aust R - registered - safety, quality, efficacy eg all medicines and analgesics Aust L - listed - low risk eg sunscreens, vitamins, herbals, fish oils
How does the liver excrete drugs?	Metabolises lipophilic drugs and excretes into bile to be excreted in faeces
How do the kidneys excrete drugs?	Filtrates hydrophilic drugs or metabolites and excretes in urine.
How will non-competitive antagonism display on a concentration-response curve?	There will be a rightward shift of the concentration-response curve with different slope and maximum response
What are the three pharmacokinetics processes that determine how much of a drug reaches its target site of action?	Absorption, distribution, elimination.
When drugs are administered orally and dosed on a chronic basis, which two pharmacokinetic parameters determine the steady-state concentration?	Bioavailability and clearance.
Which pharmacokinetic parameter is used to calculate the loading dose of a drug?	Volume of distribution
Drug X is known to prolong gastric emptying time. Would the oral absorption of another drug, such as paracetamol, be faster or slower than if taken with Drug X?	Absorption would be slower because the faster the gastric emptying, the faster the drug reaches the intestine in which it can be absorbed.
Explain why the oral dose of morphine is about 4 times larger than an intravenous dose.	Morphine has a high rate of hepatic first-pass, so less enters the bloodstream if given orally.
Drug X is excreted mainly via the urine. What is the main clinical consequence of decreased clearance of drug X by the kidney? What patient factors would be most likely to cause the decrease in clearance by the kidney.	The kidneys secrete whole, unmetabolised drug particles, so if they are filtered back into the bloodstream they'll cause prolonged effect and increased concentration which could lead to toxicity. Kidney failure, ageing and some medications may cause this.
A drug (half life = 6 hours and clearance of 1000 ml/hour) is administered as 600 mg intravenously every 6 hours. A. At what time will steady-state concentrations be reached? B. If the dose rate does not change but the clearance is halved, what happens to steady-state concentration?	Steady state is always reached in 5 half lives. 5 x 6 hr = 30 hr. Css = dose rate / clearance, so Css doubles
How is new dose rate calculated?	Normal dose rate x % of normal kidney function.
If clearance decreases, half life increases.	...
How might liver disease affect dosage requirements of high first pass drugs?	First pass is decreased so more of the drug gets through, therefore dosage must be decreased. Clearance is also reduced. Morphine - may be reduced by 200%. Steady state concentration = (bioavailability x dose rate) / clearance.
List five factors to consider when dosing for elderly patients.	1. Slower gut function = slower absorption 2. Decreased renal function = decreased renal clearance 3. Decreased liver function = decreased liver enzyme activity 4. Increased sensitivity to psychoaffective drugs (CNS) 5. Decreased homeostasis = hypertensive drugs may cause postural hypotension (stand slowly etc to avoid)
State the main factor to consider when dosing for paediatric patients.	1. Hepatic and renal clearance is greater on dose per kilo than in adults = they're not just scaled down adults 2.
What effects can drugs have during different stages of pregnancy?	1st trimester: foetal damage 2nd & 3rd trimester: decreased growth and development
What is a category A drug?	A drug taken by a large number of pregnant women with no malformation or other harmful effects on the foetus e.g. paracetamol
What is a category B1 drug?	A drug taken by a limited number of pregnant women with no malformation or other harmful effects on the foetus. Animal studies show no toxicity e.g. amoxycillin
What is a category B2 drug?	A drug taken by a limited number of pregnant women with no malformation or other harmful effects on the foetus. Animal studies are inadequate but show no toxicity e.g. dicloxacillin
What is a category B3 drug?	A drug taken by a limited number of pregnant women with no malformation or other harmful effects on the foetus. Animal studies show toxicity e.g. trimethoprim
What is a category C drug?	Drugs which owing to their pharmacological effects have cause or have been suspected of causing harmful effects on the foetus with no malformation e.g. ibuprofen
What is a category D drug?	Drugs which have caused or are expected to cause an increased incidence of foetal malformation or irreversible damage e.g. fluconazole
What is a category X drug?	Drugs which have a high risk of causing severe foetal damage e.g. oral isotretinoin
List three factors to consider when dosing in pregnancy.	1. Decreased gut motility = slowed absorption 2. Increased kidney function = increased clearance = increased dose needed 3. Increased hepatic function = increased enzyme activity = increased metabolism
Define pharmacogenetics	How people respond to drugs determined by their genetic makeup. Cannot be changed as diet and lifestyle factors can.
List three genetic factors that can vary to affect response to drugs	- metabolising enzymes - transporters - receptors
What is CYP2D6? How may pharmagogenetics affect this?	An enzyme which partially or fully metabolises 25% of all drugs on the market. Some people (5-10% of Caucasians) have different mutations in their 2D6 making it shorter and ineffective in metabolism (poor metaboliser). 2-5% of Caucasians are ultra rapid metabolisers meaning they have multiple copies of this gene and may metabolise it much faster.
What is OATP1B1? How may pharmacogenetics affect this?	An organic anion transporting polypeptide B1 to liver. An uptake transporter. Mutation in transporter stops statin drug getting to liver, accumulates in bloodstream, muscle pain.
How can a patient with gene mutations be dosed?	Azathioprine - immunosuppressant used in organ transplants, Crohn's, rheumatoid arthritis, exzema. Major toxicity is suppression of bone marrow leading to low WBC production.
What is TPMT?	An enzyme in the liver.
Name the four regulatory proteins targeted by drug therapy.	1. Carriers 2. Enzymes 3. Receptors 4. Ion channels
What is one carrier protein targeted by drug therapy?	Serotonin reuptake inhibitor (SSRI) for depression - neurotransmitter carrier protein targeted.
Name 4 receptor types targeted by drug therapy.	1. Ligand gated ion channels 2. G-protein (guanosine binding protein) coupled 3. Enzyme (tyrosine kinase linked) 4. Nuclear
Describe ligand gated ion channels.	- 4 or 5 subunits which form an ion channel in the cell membrane - binding of agonist drug opens the channel - fast response (milliseconds)
Describe g-protein coupled receptors	- 7 transmembrane segments located in cell membranes throughout the body - activation of intracellular messengers through g-protein - fast response (seconds) - > 50% of drugs
List 5 g-protein coupled receptors	1. Adrenoceptors 2. Histamine receptors 3. Serotonin receptors 4. Opioid/opiate receptors 5. Dopmine receptors
Describe enzyme linked tyrosine kinase receptors	- large extracellular ligand binding domain linked to a tyrosine kinase intracellular domain located in cell membrane - phosphorylation of proteins in cytoplasm = altered enzyme activity - slow response (minutes to hours)
Describe nuclear receptors	- large monomeric proteins located in cell nucleus - binds to hormone responsive elements of DNA to regulate transcription - slow response (hours)
Give two examples of ion channels being targeted in drug therapy.	1. Calcium channel blocker = antihypertensive 2. Sodium channel blocker = antiepileptic
What does an agonist do?	Activates receptors to mimic effects of endogenous ligands (few used clinically).
What does an antagonist do?	Blocks or diminishes normal receptor functions (most drugs that act on receptors are antagonists).
Define affinity, efficacy, tolerance and tachyphylaxis	Affinity: potency - how strongly a drug binds to a target Efficacy: maximum effect a drug can have Tolerance: effect reduced as duration of repeated exposure to drug continues Tachyphylaxis: loss of responsiveness after repeated exposure to drug
Define desensitisation, up-regulation and down-regulation	Desensitisation: decreased response of receptor second messenger system Up-regulation: increased receptor number, receptor super sensitivity Down-regulation: decreased receptor number, loss of response
Describe drug CR curve	Concentration-response curve determines drug's potency.
Define Emax	Maximum response when all receptors are occupied. Once receptors are saturated effects will not increase any further.
Define and explain volume of distribution.	The theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. It is defined as the distribution of a medication between plasma and the rest of the body after oral or parenteral dosing.
Describe S2, S3, S4, S8.	S2: Pharmacy medicine (eg cough and cold) S3: Pharmacist only (eg metered dose asthma aerosols) S4: Prescription drugs (eg antibiotics, antidepressants, vaccines) S8: Controlled drugs (eg morphine)
Define dependence	Preoccupation with obtaining and using drug of choice for its psychoactive effects- continued administration to prevent withdrawal syndrome.
Define opoid	all substance (naturally derived from opium, endogenous, synthetic) that have morphine-like effects
Define benzodiazapines	also known as minor tranquillisers or benzos- similar chemical structure and includes diazepam
Name two drugs derived from natural sources	1. Taxol (paclitaxel) derived from Pacific yew tree to treat breast and ovarian cancer 2. First ACE inhibitor developed from snake venom
Explain HTS in drug development	High Throughput Screening - a way of using lots of cells in a lab to give you a quick idea of whether new chemicals developed in a chemical library will give you a better drug or not
Notes on pre-clinical testing	Time consuming (2‐5 years) • Expensive ( $100 million / successful drug) • Uses many animals • Effects on animals may not translate to effects on humans • Rare effects may not be detected
4 phases of clinical drug development	1. To identify proper dosing and side effects. Use ~ 20‐100 healthy volunteers 2. Provides information on how well the treatment works in a clinical situation. 100‐500 patients 3. Compare the new drug with existing treatments. Must show some benefits compared to any existing treatments and be cost‐effective. 1000‐5000 patients 4. Approval by TGA, continued safety monitoring
Describe S5, S6, S7 and S9 drug classification	S5: Caution eg household poisons, weed killers, garden sprays S6: Poison eg garden pesticides, solvents, strong acids S7: Dangerous poison - arsenic, commercial pesticides. Available only to specialised/authorised users. S9: Most recreational substances eg cannabis, heroin - not alcohol or tobacco
List everything that must feature on prescriptions	- patient's name - name & address of practitioner – drug name – drug form (tablets, capsules etc) – drug strength – drug quantity – dose & frequency of administration – signature of prescriber – date of prescription
EC50	drug concentration when 50% of max response observed
Determine maintenance dose rate (mg/hr)	target concentration (mg/L) x clearance (L/hr)
Determine concentration	Dose rate / clearance
What is t1/2 and how is it calculated?	(0.69xvolume of distribution) / clearance
Determine loading dose (mg)	concentration (mg/L) x volume of distribution (L)
Determine kidney disease dose	Normal dose x percentage of normal kidney function
4 manufacturer instructions for the storage and handling of drugs	Temperature, light, moisture, shelf life
Define hazard	The intrinsic capability of a substance to cause an adverse effect
Define Risk assessment	Process whereby hazard, exposure and risk are determined
Define risk	The probability that a hazard will cause an adverse effect under specific exposure conditions
Define alimentary route	Dissemination of microorganism via eating routes. contaminated oral medication.
Name the two routes of biological hazards	Alimentary and airborne
Cytotoxic drugs	Intended primarily for the treatment of cancer. Known to be highly toxic to cells, principally through their action on cell reproduction.
When may exposure to cytotoxic drugs occur?	Drug prep Drug administration Patient care activities spill management waste management
Steps in risk management	Identify hazards, assess risks, decide on control measures, implement control measures, monitor and review effectiveness of control measures.
Define standard operating procedures (SOPs)	Essential that written procedures are developed for all work activities involving dangerous drugs and waste, including plant and equipment cleaning, inspection and maintenance
How to limit exposure to drugs during preparation	Avoid skin contact, liberation of aerosols or powdered drug into the air, cross contamination
List 4 tips to limit exposure to drugs	- allow enough time to administer complicated drug regimes - administer and prepare with another staff member - know who to contact within the healthcare environment if something goes wrong - quick and effective management of incidents can prevent further adverse outcomes
What categories are blood and body fluid exposure divided into?	Mucocutaneous (skin) and percutaneous (under skin)
Most common mucocutaneous fluids and body surface exposed	Blood or blood products, eyes and skin
Most common percutaneous exposure	NSI/sharps, hollow bore needle after use and before disposal
Management of NSI/sharps injury	Bleed the wound, wash with soap and water or antiseptic, remove embedded materials
Management of mucous membrane contamination	Flush (eyes) with normal saline or water, remove contact lenses after flushing an clean as usual
Nurse's role in disposal of medication	Documentation Medication returns dealt with by pharmacy Oral meds in unbroken blister packs may be reused within hospital Bottles of oral med never reused Notification of expiry date/return to pharmacy Broken or tampered return to pharmacy
What are the NPS 4 steps of medication management?	1. Assess the patient - get an accurate and current history, review meds, conditions and comorbidities, evaluate physical and cognitive function, recognise changing health, vulnerability and life expectancy 2. Check medicines - identify benefits and risks to the individual 3. 4. ***********
study medication management cycle and medication chart from second week 11 lecture on med management	...
How many regular drugs are patients normally on?	11
Review drug errors percentages	....
How many PRN medicines have an unclear abbreviation?	1 in 5
Type A - augmented Type B - bizarre	...
Who is at risk of having an adverse drug reaction?	Women, elderly, children, immunocompromised, concurrent diseases, genetic factors, previous reactions, organ failure
What are the clinical signs of someone experiencing an ADR?	Rash, drowsiness, vomiting, swelling, anaphylaxis, difficulty breathing, neurological changes, change in HR and BP
Describe the biological hazards that can occur when administering medicines.	- droplet contact - NSI - airborne - vehicle contact - alimentary
Describe three of commonly used approaches when dealing with a non-cooperative patient refusing to take medication	- ask why they don't want to take it - explain why they need to take it - leave it and come back - be sympathetic - direct instruction - positive reinterpretation
What criteria is NOT preferred with regard to a newly developed drug	It has low lipid solubility
The first human (clinical) studies for a new drug to treat high blood pressure would be best performed in?	A small group of healthy people
What criteria is preferred with regard to a newly developed drug? (3 things)	It is effective against a target protein, it does not cause serious ADRs, it can be manufactured in large scale quantities
Digoxin is a drug with a narrow therapeutic index. A. Define the therapeutic index of a drug. B. What is the clinical consequence of giving a dose of digoxin that results in plasma concentrations above the therapeutic range?	A: the plasma drug concentration range or the dose that provides efficacy without toxicity. B: Adverse effects, e.g. nausea, vomiting, diarrhoea, blurred vision, headache, dizziness, confusion, arrhythmia.
What are the three pharmacokinetics processes that determine how much of a drug reaches its target site of action?	Absorption, distribution and elimination
When drugs are administered orally and dosed on a chronic basis, which two pharmacokinetic parameters determine the steady-state concentration?	Bioavailability and clearance
Which pharmacokinetic parameter is used to calculate the loading dose of a drug?	Volume of distribution
Drug X is known to prolong gastric emptying time. Would the oral absorption of another drug, such as paracetamol, be faster or slower than if taken with Drug X?	slower - absorption of all drugs is dependent on gastric emptying time
Explain why the oral dose of morphine is about 4 times larger than an intravenous dose.	morphine has high rate of metabolism in liver, less reaches systemic circulation when taken orally because morphine has this high first pass effect
Drug X is excreted mainly via the urine. What is the main clinical consequence of decreased clearance of drug X by the kidney? What patient factors would be most likely to cause the decrease in clearance by the kidney.	Accumulation of drug X in plasma and increased potential over time of toxicity. Kidney disease, ageing (the elderly), some medicines
A drug (half life = 6 hours and clearance of 1000 ml/hour) is administered as 600 mg intravenously every 6 hours. A. At what time will steady-state concentrations be reached? B: If the dose rate does not change but the clearance is halved, what happens to steady-state concentration?	A: 5 half lives = 5 x 6 hr = 30 hr B: Css = dose rate / clearance, so Css doubles
Drug A and Drug B have the same drug target and each causes dry mouth as an adverse effect. What is the main clinical consequence of an interaction when Drug A and B are used together?	effect of drugs A and B is potentiated to cause a very dry mouth
Which of the following foods: milk, grapefruit juice, yoghurt, potatoes can alter A: the absorption of drugs B: the bioavailability of drugs	A: milk and yoghurt B: grapefruit juice
What additional requirements for prescribing, storage and dispensing of S8 controlled drugs such as morphine are needed?	Prescribing: quantity written as numerals and in words Storage: stored in a safe Dispensing: log book records patient details against drug and its strength, number of items remaining in safe, checked and signed by pharmacist and countersigned by a pharmacist or nurse.
What patients are at a higher risk of experiencing an adverse drug reaction and what are the clinical signs of someone experiencing an adverse drug reaction?	Elderly, sex (females), concurrent diseases, genetic factors, previous drug reaction, route of administration, dose, duration and frequency difficulty breathing, lethargy, changes in colour, rash, nausea/vomiting, change in HR and BP, neurological changes
Describe the biological hazards that can occur when administering medicines and how?	contact from tissues, fluid and other body substances Airbourne & Alimentary route Droplet, direct and indirect contact Vehicle transmission
List a few chemical-drug interactions that cause drug dosing to have to change	Medicines, herbal substances, foods, environmental chemicals
Discuss enzyme induction	When one drug (A) stimulates the drug metabolising enzymes of another drug (B). This causes lower concentrations of drug B and lower efficacy, potential to morbidity/mortality. Drug B dosing must be increased, but decreased when drug A is ceased so as not to cause toxicity.
Discuss enzyme inhibition	When multiple drugs compete for the same drug metabolising enzyme site in the liver. If drug A blocks the metabolism of drug B, drug B concentration won't decrease, and if this drug has a narrow TI it can be toxic. Dosage adjustment to decrease drug B dosing. Especially important if drug B has a high hepatic first pass rate.
Give an example of a strong herbal liver drug enzyme inducer and explain its effects with an example	St John's Wort (mild antidepressant) lowers blood concentrations of many other drugs such as cyclosporin, an immunosuppressant. St John's Wort and cyclosporin cannot be given together or a transplant may be rejected.
Give an example of an oral absorption interaction	Antacids can reduce the GI absorption of many drugs such as antibiotics. Antacids should not be taken at the same time as other medications.
Give an example of a food-drug interaction	Grapefruit and grapefruit juice. Ingredients in the juice are powerful blockers of drug metabolising enzymes in the GIT. A drug metabolised in the GIT (e.g. statins for lowering cholesterol) will not be metabolised, leading to higher concentrations of the drug - muscle pain.
Give an example of an environment-drug interaction	Cigarette smoke induces a specific drug metabolising enzyme (CYP1A2) in the liver. Caffeine is almost exclusively metabolised by CYP1A2, therefore cigarette smoke and caffeine together will increase caffeine clearance. Smokers tend to drink more caffeine.
Explain pharmacodynamic mechanisms of drug interactions	Potentiation of the effect: when drug A and drug B act on the same target, e.g. amitriptyline (antidepressant) and ipratroprium (anti asthmatic) reach several targets, one of which causes dry mouth as a side effect. If a patient is taking both, result is a very dry mouth. Some drugs act on a different target but have the same effects, e.g. CNS depressants and alcohol lead to increased sedation.
How might drug-drug interactions affect an organ?	Eg drugs used for hypertension, diuretics and NSAIDs reduce renal function. In combination, "triple whammy" - commonly taken in elderly patients, lead to renal failure.
List some features found with product information of a drug	Pharmacology, indications, interactions, contraindications, precautions, adverse effects, dosage and administration, overdosage, storage instructions, poison schedule, name and address of sponsor, date of approval
What details must a prescription feature?	- pt name, address, phone number - prescriber's name and address - drug name (generic) - drug form (tablets, capsules etc) - drug strength - drug quantity - dose and frequency of administration - repeats if any - signature of prescriber - date of prescription
What additional information must feature on a prescription for a controlled drug?	- pt DOB - qty to be dispensed in words and numerals
What is the role of the pharmacist when dispensing medication?	- checks drug name, dose, strength, interactions - finds out if pt has had drug before - prints label with all instructions for use
What details are recorded in a controlled drug log book?	- pt details w/ drug strength/dose/date - no. of items/tablets/capsules remaining in safe
What is the difference between an adverse drug event, an adverse drug reaction, and a side effect?	ADE: overdose/medication error, i.e. one of the six rights is wrong ADR: can be caused by an ADE, an unexpected reaction, can occur in normal dosing, preventable Side effect: expected possible **not used, too vague
Types of ADR	Augmented: intolerance eg diarrhoea, mild due to pharmacological action of the drug Bizarre: allergy, not related to dose, unpredictable, usually immunological origin Continuing: usually dose and time related, i.e. about total cumulative dose e.g. tolerance to opioids Delayed: becomes apparent some time after use, e.g. developing cancer from immunosuppressants, may occur years later End of use: withdrawal
Frequency definitions	Very common: >10% Common 1-10% Uncommon or infrequent 0.1-1% Rare: between 1 in 1000 and 1 in 10,000 Very rare: <1 in 10,000
Common causes of non-compliance	• Polypharmacy; Confusion over complicated drug regimens • Bad taste or pain on administration • Adverse Effects (Real or Perceived) • Poor communication and lack of information about treatment • Lack of support and monitoring of therapy • Cost or difficulty in obtaining medicines
Risk factors for patient being noncooperative	Environment, lack of stimulation, lack of movement • Progression or worsening of disease state • Newlydiagnoseddisease • Infection • Reactiontotreatment/medication • Allergy • Anxiety/ recognition of own mortality
What to do when a pt refuses medication	1. Do nothing 2. Be calm and soothing 3. Separation/privacy 4. Explain 5. Positive reinterpretation 6. Direct instruction
Types of IV therapy	• Ambulatory infusion pumps • Central venous access devices • Diabetes insulin infusion pump • Enteral feeding pump • Implantable pumps • Large volume infusion pumps • Peripheral venous access devices • Syringe infusion pumps

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	Created by Elizabeth McQuie over 7 years ago