Pharmacology And Medications Flashcards
Name a drug for hormone therapy in breast cancer and explain it s function
Tamoxifen - targets breast cancer cells with oestrogen receptors
Name a drug for treating breast cancer which has HER2 receptor
Herceptin
define hypersensitivity
reaction to an allergen which in the same dose is tolerated by normal subjects
explain the pathophysiology of type 1 hypersensitivity
Prior exposure to the antigen/drug
IgE antibodies formed after exposure to molecule
IgE becomes attached to mast cells or leucocytes, expressed as cell surface receptors
Re-exposure causes mast cell degranulation and release of pharmacologically active substances such as histamine, prostaglandins, leukotrienes, platelet activating factor etc
explain type 2 hypersensitivity reactions
Drug or metabolite combines with a protein
Body treats it as foreign protein and forms antibodies (IgG, IgM)
Antibodies combine with the antigen and complement activation damages the healthy cells e.g. rheumatoid arthritis
Type 2 hypersensitivity is like a case of mistaken identity in the body. It happens when the immune system mistakenly targets healthy cells or tissues, thinking they’re harmful. This can lead to various conditions where the body attacks its own cells or cells perceived as foreign, causing harm or damage. Examples include autoimmune disorders like rheumatoid arthritis or certain types of anemia.
explain type 3 hypersensitivity
Antigen and antibody form large complexes and activate complement
Small blood vessels are damaged or blocked because of accumulation of these complexes. Accumulation of these deposits also triggers inflammation as leucocytes are attracted to site.
Ex.: glomerulonephritis, vasculitis.
explain type 4 hypersensitivity
Antigen specific receptors develop on T-lymphocytes
Subsequent administration leads to local or tissue allergic reaction and subsequent formation of granulomas.
E.g. contact dermatitis
E.g. Stevens Johnson syndrome (TEN)
what are the symptoms of anaphylaxis
must say rash, swelling of lips face oedema, central cyanosis, wheeze, hypotension, cardiac arrest
what is the ABCDE approach and how do you examine each
airway - involves assessing the patient’s airway to ensure it’s open and unobstructed. If there’s a blockage or if the patient is having difficulty breathing, immediate interventions such as clearing the airway or placing an artificial airway
breathing - Evaluate the patient’s breathing pattern, rate, and oxygenation. Ensure adequate ventilation, and address any respiratory distress or signs of inadequate breathing. Interventions might include providing supplemental oxygen, assisting ventilation, or treating underlying causes of respiratory failure.
circulation - Assess the patient’s circulation, including their pulse, blood pressure, and signs of adequate perfusion. Treat any signs of shock or inadequate blood flow, such as administering fluids, medications to support blood pressure, or interventions to improve cardiac function if needed.
disability - evaluating the patient’s neurological status, including their level of consciousness, neurological deficits, or signs of altered mental status.
exposure - checking the patients for wounds and things and also look around to see if the environment is safe for the patient so that you can take action if required
what are common triggers of anaphylaxis
peanuts
cow’s milk
gluten
antibiotics
chemotherapy drugs
contrast media
NSAIDs
insect venom
describe the late response in anaphylaxis
happens a couple hours after the initial response –> due to the recruitment of more inflammatory mediators you get a second anaphylactic episode
what is the management of anaphylaxis
Commence basic life support. ABC
Stop the drug if infusion
Adrenaline IM –> 500micrograms(300mcg epi-pen)
High flow oxygen
IV fluids – aggressive fluid resuscitation
If anaphylactic shock may need IV adrenaline with close monitoring
Antihistamines not first line treatment but can be used for skin symptoms
Corticosteroids no longer recommended
Lie sitting or flat to breathe more easily
Lift legs to help fluid circulate prevent oedema
how does adrenaline affect all adrenergic receptors
alpha 1 receptors
Vasoconstriction - increase in peripheral vascular resistance, increased BP and coronary perfusion
Reduces oedema
Beta1-adrenoceptors
positive ionotropic and chronotropic effects on the heart
Beta 2 adrenoreceptors bronchodilates
alpha 2 adrenoreceptors
Attenuates further release of mediators from mast cells and basophils by increasing intracellular c-AMP and so reducing the release of inflammatory mediators (the negative feedback loop)
what do you do if a patient has refractory anaphylaxis
refractory anaphylaxis –> no improvement in symptoms despite 2 doses of IM adrenaline
give IM adrenaline every 5 min until IV adrenaline infusion is started
high flow o2
monitor heart for cardiac arrhythmia
what blood test is used to confirm anaphylaxis and why
mast cell tryptase because it shows rate of mast cell degradation
risk factors for hypersensitivity
Females > Males
EBV (Epstein barr virus)
HIV
Previous drug reactions
Uncontrolled asthma
Certain HLA groups
liver metabolism
what are μ receptors
one of the three main types of opioid receptors found in the body. Activation of the μ receptor plays a significant role in mediating the effects of opioid drugs.
A 60 year old woman presents to her General Practice with tiredness and dry skin. She is found to have hypothyroidism and is started on oral levothyroxine 75mcg tablets, 1 tablet daily.
Levothyroxine tablets have a variable bioavailability between individuals.
Which of the following is most likely to cause a reduction in bioavailability?
A) Short bowel syndrome
B) Reduced renal function
C) Low albumin
D) Hepatic impairment
E) Low body weight
A
Bioavailability is the proportion of the substance that enters the bloodstream
A pharmaceutical company is developing a new drug (drug x) for the treatment of heart failure. The half life (t1/2) of drug x is found to be 6-10 hours (average 8 hours).
Which of the following could increase the half life (t1/2) of a drug?
A) Co-administration of a CYP450 enzyme inducer
B) Impaired absorption from GI tract
C) Increasing the administered dose
D) Changing formulation from oral to IV
E) Renal impairment
E
Which of the following types of drug interactions would result in an increased therapeutic effect and potential drug toxicity?
A) Amiodarone displacing warfarin from plasma albumin
B) Bisoprolol opposing the action of salbutamol at β2 receptors
C) Oral iron forming an insoluble drug complex with doxycycline
D) Phenytoin inducing the CYP450 enzyme which metabolises warfarin
E) Rifampicin inducing Pgp which transports rivaroxaban
A
Drug y is an antagonist at B1 receptors. Which of the following adverse drug reactions is a B1 antagonist most likely to cause?
A) Tremor
B) Bradycardia
C) Urinary retention
D) Hypertension
E) Dry mouth
B
Which type of adverse drug reaction is most likely to be identified during clinical trials?
A) Bizzare
B) Delayed
C) Chronic
D) Augmented
E) Genetic
D
Match the following pharmacodynamic mechanisms with the most likely adverse drug reaction:
Bradycardia
Tremor
Pupil constriction.
Constipation 𝜇 agonism
Urinary retention
M3 antagonism
M3 agonism
𝛽2 agonism
𝛽1 antagonism
𝜇 agonism
Bradycardia 𝛽1 antagonism
Pupil constriction M3 agonism
Urinary retention M3 antagonism
Tremor 𝛽2 agonism
what is the difference between first order and second order kinetics
first order –> constant % drug is eliminated over time –> trend is exponential for drug plasma conc/time
second order –> constant amount of drug is eliminated over time –> trend is inverse proportional for drug plasma conc over time
what is a modified release drug
medication designed to release active ingredients in a controlled or extended manner
what are the different types of modified release drugs
extended-release - slow release over time
delayed-release - release drugs at a specific location in the GI
pulsatile-release - release of drug at specific intervals
what effect does modified release doing have on the maximum plasma concentration
it decreases it because it slows down the absorption of the drug
how is the half-life of an IV drug affected if you give it at half the dose
it is not affected
what does the half-life of a drug depend on
clearance and Vd of the drug
how long does is take to clear 97% of a drug from the body in half lives in a first order kinetics drug
5 half lives
what kind of drugs are more likely to give withdrawal symptoms; short or long half life
short half life
what is the steady state in drug administration
the point at which the rate of drug input = the rate of drug elimination
you are administering a drug of first order kinetics
if you give a continuous IV infusion how long does it take in half lives till you reach steady state
5 x half life –> because you need to start eliminating the drug to reach a steady state
what effect does a 50% dose reduction in an iv infusion have on drug plasma concentration at steady state and the time required to reach steady state
drug plasma concentration –> reduction to half
time required to reach ss –> unchanged
what effect does reduced clearance have on half life, time needed to reach steady state, and plasma concentration at steady state.
they will all increase
what is a loading dose
providing an initial larger dose of a drug to ensure a quick therapeutic response –> used in emergencies
A 66 year old woman is admitted to A&E with SOB and haemoptysis.
CTPA confirms bilateral PEs. She is prescribed an IV loading dose of unfractionated heparin 5000 units followed by an IV continuous infusion. What effect will the loading does have on the heparin pharmacokinetics?
a) reduce half life
b) increase bioavailability
c) reduce time to steady state plasma conc
d) increase Vd
e) reduce drug clearance
c
what is druggability
a target in our bodies that is known to have high affinity for binding drugs and which upon binding with the drug acts with a therapeutic benefit to patient
what are potential drug targets
receptors
enzymes
transporters
ion channels
what are statins
cholesterol lowering drugs
what are the 4 types of receptors
ligand-gated ion channels
G protein coupled receptors
Kinase-linked receptors
Nuclear receptors
what is potency
the amount of drug that you need to cause a maximal response
what are all of the types of histamine receptors and their roles
H1 - allergic reactions
H2 - gastric acid secretion
H3 - associated with CNS disorders
H4 - immune system and inflammatory conditions
what is EC50
the concentration that gives half the maximal response
what are receptor affinity and efficacy
affinity - how well a ligand binds to a receptor
efficacy - how well a ligand activates a receptor
how i potency measured
via EC50
what is inverse agonism
when a drug bonds to the same receptor as an agonist but produces the opposite response to the agonsit
what happens to receptors as tolerance is achieved
the receptors are downregulated so you would need higher doses of the drug to achieve the same response
what is efficacy in pharmacology
the maximum achievable response form a drug-receptor interaction
how fast does opioid withdrawal start
within 24 hours
what is a receptor reserve
spare receptors –> some drugs don’t need to interact with all receptors to achieve a maximal response in the system
what is an antagonist of nicotinic receptors and what effect would you think that it would have on the patient
curare
a neuromuscular blocking agent that blocks the action of acetylcholine at the neuromuscular junction, leading to muscle paralysis
what is an antagonist of muscarinic receptors and what effect would it have on a patient
atropine
stops parasympathetic activity (patient will get increased HR, dialeted pupils, increased BP, decreased saliva secretion)
what are the clinical uses of glucocorticoids
SKIN COND
skin eczema and psoriasis
BREATHING COND TO DILATE BRONCHI
asthma, allergies, COPD
INFLAMMATION SURPRESSION
inflammatory bowel disease
inflammatory arthritis (rheumatoid arthritis)
meningitis
AUTOIOMMUNE STUFF
MS
GLUCOCORTICOID DEFICIENCY
adrenal failure
how do glucocorticoids affect BP
Glucocorticoids influence blood pressure by regulating the sensitivity of blood vessels to other hormones like adrenaline and by affecting the reabsorption of water and salts in the kidneys; increases salt reabsorption and hence increases water reabsorption too
what do statins inhibit and why
HMG-CoA reductase because it is the enzyme of the rate-limiting step in the cholesterol pathway
what categories of medications can you prescribe to decrease BP
ACE inhibitors
Angiotensin 2 receptor blockers
Alpha-blockers
Beta-blockers
Calcium channel blockers
Diuretics
(Think AAABCD)
what is amlodipine, how does it work, and what are its effects
amlodipine = angioselective calcium channel blocker
it stops the movement of calcium ions in smooth muscle cells and cardiac muscle cell
effects: decreases HR, dilates blood vessels, reduces SVR, decreases BP
what class of enzyme inhibitors are omeprazole and asprin
irreversible enzyme inhibitors
what % of oral morphine is metabolised by first pass metabolism
50%
what are possible routes of administration of opioids
transdermal, IV, oral, epidural, IM
what type of receptors do opioids work on how do they work
G-coupled receptors
they inhibit pain signals at the spinal cord and midbrain
what are side effects of opioids
respiratory depression, sedation, nausea, vomiting, constipation, itching, immune suppression, and endocrine effects.
what is the medical term for prolonged correction
priapism
which are the cholinergic receptors
muscarinic and nicotinic
what are the 3 determinants of BP
HR, SVR, SV
what are vasopressors and what receptor do they act on
drugs which cause vasoconstriction; they act on alpha 1 receptors
what are the medications which you need to prescribe to obese people?
1) anti-coagulants
- aspirin (anti-platelet)
- warfarin (anti-coagulant)
2) cholesterol inhibitors
- statins
3) anti-hypertensives
- ACE inhibitors
4) heart rate regulators
- beta-blockers
what are the actions of alpha 2 agonists
they reduce the effect of the sympathetic system –> they reduce BP and HR and they can act as sedatives and analgesics
give an example of a alpha 2 agonist
clonidine
how often can you repeat adrenaline and what is the dose for an anaphylaxis IM injection
every 3-5 minutes
0.5mg IM
what is the dose of IV adrenaline for a cardiac arrest
1mg IV
name two specific a1 agonists
phenylephrine
metaraminol
name two a2 agonists
clonidine
dexmedetomidine
name a beta 1 agonist
dobutamine
name a beta 2 agonist
salbutamol
name a general agonist of adrenergic receptors
adrenaline
what are the subgroups of nicotinic receptors?
ganglionic, neuromuscular, and CNS
what are signs of acetylcholinesterase inhibitor toxicity
midriasis - dialated pupils
tachycardia
weakness
hypertension
fasciculations
what are the different types of muscarinic receptors
M1 - increases motility and secretions in gut –> helps facilitate CNS effects
M2 - Cardiac
M3 - Exocrine glands and smooth muscle
M4 - CNS
M5 - CNS
name an antagonist of nicotinic receptors
trimethaphan
name 4 antagonists for muscarinic receptors
atropine
glycopyrrolate
hyoscine
ipratropium
name agonists of nicotinic receptors
nicotine and Ach
define pharmacodynamics
effect of a drug on the body
define pharmacokinetics
the FATE of the drug in the body
what are the 4 main steps of pharmacokinetics?
absorption, distribution, metabolism, excretion
what is an IT route of administration
intrathecal - administered into the spinal theca
what is the difference between topical and transdermal penetration
the medication is applied on the surface of the skin or mucous surfaces but in topical it stays on skin (eg.: sunscreen), and in trnasdermal it penetrates through skin
what factors affects drug absorption
lipid solubility
drug ionisation —> ionisation decreases solubility
route of administration —> if drug has to pass first-pass metabolism it needs to resist the strong pH of the stomach to get absorbed in the intestines
what are the factors affecting oral drug absorption
gastric enzymes
low pH
food —> will slow down gastric emotying and hence decrease absorption
gastric motility
previous surgery
drug properties (lipid soluble/ionised/hydrophillic)
if the drug has a capsule for modified release
interaction with P-gp!!! —> moves drugs back out of the GI
what is bioavailability
the proportion of administered drug that actually reaches the systemic circulation
what affects drug distribution
molecule size
lipid solubility
protein binding
what does “Vd” stand for
Volume of distribution —> volume of plasma required to contain the administered dose
why is it hard for drugs to reach the CNS
BBB
in what ways can drugs reach the CNS
High lipid solubility
Intrathecal administration
Inflammation
what enzyme does the phase 1 metabolism of drugs depend on
CYP450
what are phase 1 and phase 2 reactions
phase 1 - oxidation, reduction, hydrolysis (reactions catalysed by CYP450)
phase 2 - conjugation of a functional group to produce a hydrophilic molecule so that it can be excreted in urine (ex.: glucuronidation, sulfation, methylation)
what are synergistic pharmacodynamic interactions
when 2 substances combine to produce an effect greater than the sum of their individual effects
what affects renal excretion of drugs
GFR
Active tubular secretion —> where the peritubular capillaries actively secrete the toxins and drugs in the nephron tube
Passive reabsorption
what is an induction drug and give an example
a drug given to put a patient to sleep
ex.: propofol and thiopentone
which is the most effective form or renal clearance and how is it carried out
Active tubular secretion and via OAT or OCT
give an example of an important drug-food interaction and explain why
warfarin or statin taken with GRAPEIT juice
grapefruit juice is a CYP3A4 inhibitor which is supposed to metabolise those meds.
milk can affect the absorption of some drugs (doxycycline antibiotic) due to the formation of insoluble complexes with Ca
warfarin can’t be taken with foods high in vit K as warfarin is a vitamin K antagonist
warfarin also can’t be taken with cranberry juice as cranberry juice is a CYP2CP inhibitor
how can drug interactions be predicted and avoided
Understand the Pharmacokinetics and Pharmacodynamics of prescribed drugs.
Use Reliable Resources
Perform Thorough Medication Reviews including prescription medications, over-the-counter drugs, herbal supplements, and vitamins.
Consider Patient-Specific Factors: Individual factors such as age, gender, genetics, underlying health conditions, organ function, and other medications being taken
Educate patients about the importance of disclosing all medications to healthcare providers.
Consider Alternative Therapies: When possible, consider alternative medications or therapies that have a lower risk of interactions. Choose drugs with different mechanisms of action or routes of metabolism to minimize the likelihood of interactions.
Be Mindful of Food and Drug Interactions: Some medications interact with certain foods or beverages, affecting their absorption or metabolism. Educate patients about these interactions and advise them on appropriate dietary modifications if necessary.
Monitoring of drug action (bloods, observations)
what patients are at high risk of drug interactions
patients who take many meds –> polypharmacy
patients with kidney and liver disease
extremes of age
what are the types of adverse drug reactions and what do they mean
A - Augmented
(predictable and related to the known pharmacological properties of the drug; NOT LIFE THREATENING)
B - Bizarre
(not related to the intended action of the drug; SEVERE ex.: anaphylaxis)
C - Chronic
(due to long-term use and cumulative dose effects ex: kidney damage due to long term use of metformin)
D - Delayed
(reactions that appear a long time after starting the use of the meds and are chronic but do not necessarily require prolonged and continued use. ex.: chemotherapy-induced cancer - leucopenia)
E - End of use
(withdrawal symptoms)
F - Failure of treatment
G - Genetic
(drug causes damage to the genome)
what does the DoTS way for classifying ADRs (alternative drug reactions) stand for
dose-relatedness
timing
susceptibility
what is the yellow card
the system used to report any alternative and serious drug reactions and possible unlicensed uses of a drug
what are black triangle medicines
medicines which are subject to post-market surveillance ; all of their adverse drug reactions have to be reported
what gene encodes for MHC
HLA
what is Stevens-Jhonson syndrome
overreaction of immune system to a trigger which leads to bleeding and peeling of skin and surfaces of the eyes, mouth, and throat
what are factors thought to increase the incidence of anaphylaxis?
pollution
age
gender
changes in pollen patterns
Vit D deficiency
increase in C-section
chemicals
what are the histamine receptors and why are the important in anaphylaxis treatment
H1 Receptors –> found on smooth muscle cells, endothelial cells, and certain neurons. their stimulation causes VASODILATION and BRONCHOCONSTRICTION
they are part of the allergic response
they are important because antihistamine medications target H1 receptors to alleviate anaphylaxis symptoms like itching, sneezing and runny nose.
H2 Receptors –> mainly located on the surface of parietal cells in the stomach lining.
Activation of H2 receptors stimulates the secretion of gastric acid into the stomach.
H1 receptor antagonists, such as diphenhydramine and cetirizine, are commonly used to treat allergic reactions and symptoms.
H2 receptor antagonists, including ranitidine and famotidine, are used to reduce stomach acid production in conditions associated with excess gastric acid secretion.
There are also H3 and H4 –> function not well known
HISTAMINE 1 EXPLANATION:
Histamine, when binding to H1 receptors, can produce a variety of physiological effects, and the symptoms of sneezing and itching are attributed to specific actions in different tissues:
Sneezing:
Histamine, acting on H1 receptors in the nasal mucosa, stimulates the sensory nerves and triggers the reflex that leads to sneezing. This response is part of the body’s defense mechanism to remove irritants from the nasal passages.
Itching:
Histamine-induced itching is often related to the release of other substances, such as prostaglandins and leukotrienes, in response to histamine binding to H1 receptors on sensory nerves. These mediators contribute to the sensation of itching.
While histamine, through H1 receptors, can cause vasodilation and bronchoconstriction, the action of H1 receptor blockers (antihistamines) is more complex. Antihistamines selectively block the effects of histamine on H1 receptors, which is why they are effective in alleviating symptoms like sneezing and itching. However, they may not completely counteract all actions of histamine or may have different effects in various tissues.
Regarding vasodilation and bronchoconstriction:
Vasodilation: H1 receptor blockers can counteract histamine-induced vasodilation to some extent, particularly in peripheral blood vessels. This is why first-generation antihistamines, which can cause sedation and have some anti-cholinergic effects, may also lead to mild decreases in blood pressure due to their vasodilatory actions.
Bronchoconstriction: Antihistamines, especially first-generation ones, may not fully counteract histamine-induced bronchoconstriction. In fact, some first-generation antihistamines may cause mild bronchoconstriction in susceptible individuals. For bronchodilation, medications targeting beta-2 adrenergic receptors (beta-2 agonists) are more commonly used.
what are the medications that end in “pril”
ACE inhibitors
what are the medications that end in “sartan”
ARBs
Angiotensin 2 receptor blockers
what are the medications that end in “dipine”
Ca channel blockers
what are the medications that end in “olol”
Beta blockers
what are the medications that end in “ide”
loop diuretics
what are the medications that end in “thiazide”
thiazide diuretics