Stratum corneum of the dermis.
Lipid solubility, molecular weight, pH, local histamine release, and daily dose requirements.
Anaphylactic reactions involve an immune mechanism and require prior exposure to an antigen, while anaphylactoid reactions do not involve an immune mechanism and do not require prior exposure to an antigen.
Anaphylactic reactions are potentially life-threatening and dose-independent ('all-or-nothing').
CYP3A4 is the most abundant Cytochrome P450 isoform.
The movement of drug molecules against their concentration gradient using energy derived indirectly by coupling pump action with an actively maintained ionic gradient.
Glutamate
Increased heart rate (HR)
Sigmoid curve
LD50 is significantly higher than ED50, safer
Median lethal dose
The higher the K_D, the lower the affinity of the drug.
Fc receptors
Full IA (IA = +1).
Potent vasodilators causing hypotension, increased capillary permeability leading to oedema, and bronchospasm.
Turn off volatile anesthetics, hyperventilate with high FGF and 100% O2, start TIVA, stop surgery if appropriate, and give dantrolene as soon as possible.
To maximize activity through activation by liver metabolism
It prevents the release of Ca2+ from the sarcoplasmic reticulum and uncouples the excitation/contraction process.
J = D (ΔC * A / T)
Molecular weight (MW), lipid solubility, ionization (drug pKa, tissue pH), concentration gradient, protein binding, regional blood flow, tissue mass.
Conformational change
Diffusion coefficient
Repetitive compulsive use of psychoactive substances known by the user to be harmful.
Vessel-rich group (e.g., brain, heart, liver, kidneys, endocrine organs), muscle group, fat group, vessel-poor group (e.g., bones, teeth, hair, cartilage).
Haemolytic transfusion reaction and heparin-induced thrombocytopenia.
Lipid soluble
Exaggerated or inappropriate immune response.
Concentration gradient
Renal excretion
Lipid solubility, ionization, protein binding
Reconstitute with 60 ml of water to form an alkaline preparation.
Dibucaine number 60
Dibucaine number 20
Dissolution in the lipid bilayer and via protein channels
RYR1
Excessive efflux of Ca²⁺, generalized muscle rigidity, increased ATP consumption, increased CO₂, heat and lactate production, cell lysis, myoglobinaemia, hyperkalaemia, and acidosis
Two obligatory NR1 and two NR2 subunits
Anaphylactoid reactions are usually less severe and severity is dose-dependent.
Abrupt discontinuation of clonidine leading to rebound hypertension
The slope of the curve represents potency
Neuromuscular junction (post-junctional and pre-junctional), extra-junctional (foetal, denervation injuries and burns), neuronal (CNS, autonomic ganglia, adrenal medulla)
2 ACh molecules bind to 2 α subunits, conformational change, opening of central ion pore, cations move down their concentration and electrical gradients, membrane depolarisation
A drug that has high affinity to a receptor but no intrinsic activity
Antagonists bind to either active sites (the same as for the agonist) or allosteric sites (different to that of the agonist)
A drug that competes with the agonists for the same receptor binding site
The binding site is associated with the α subunits. GABA binding causes a conformational change.
Allergies to adhesive components, slow onset of action, variable plasma concentration in the first 24 hours, continued absorption after patch removal, overdose (damaged reservoir patch), drug abuse potential (reservoir patch), increased rate of absorption with body temperature, DC shock if pads over patch.
Pain, inflammation, pyrogenic effects, regulation of renal blood flow, increased gastric acid secretion, and increased protective mucus secretion in GIT.
Molecular weight (MW), concentration gradient, lipid solubility, pharmaceutical preparation, physicochemical interactions (food, other drugs).
Fentanyl, buprenorphine, scopolamine, clonidine, GTN.
Hyperventilate to normocapnia and administer sodium bicarbonate.
CYP3A4
Naloxone can exaggerate withdrawal symptoms, which can be abolished by a small dose of opioid.
GTP
D = S / √MW
Acute intermittent porphyria, variegate porphyria, hereditary coproporphyria.
L-tryptophan
MH Susceptible (positive to both), MH Equivocal (positive to only one), and MH Negative (negative to both).
NMDA receptors and Non-NMDA receptors
Primary exposure to an antigen leads to B lymphocytes producing specific IgE.
Area of diffusion
Henderson-Hasselbalch equation
Reduction is the addition of electrons to molecules, often driven by P450 enzymes. Examples include GTN and N2O.
Hydrolysis is a reaction where a molecule is cleaved into two parts by the addition of H2O. It is not P450 driven and involves enzymes like plasma cholinesterase and red blood cell esterases. Examples include Sch, Mivacurium, Remifentanil, and Esmolol.
At pH below their pKa
Different degree of ionisation of the same substance on each side of membrane that separates fluids with different pH
The movement of drug molecules against their concentration gradient using energy.
A drug whose antagonistic effect can be reversed by a higher concentration of the agonist. Efficacy is unaffected (Emax is unchanged) while potency is decreased (ED50 is increased).
The concentration of the drug that produces 50% of the maximum effect.
Quantal (all-or-nothing) dose-response curve
Protein binding is a reversible and saturable process with very fast rates of binding and release (milliseconds).
Ionised drugs do not bind to proteins.
Molecular weight (MW), lipid solubility, ionisation, protein binding, tissue binding outside plasma, patient factors (age, pregnancy, disease).
A known dose of a drug is given at time 0, blood samples are collected and drug concentrations are measured, a semi-logarithmic plot is drawn, and C0 (plasma concentration at time 0) is extrapolated back to the y-axis. Vd = dose / C0.
Effect
Arachidonic acid.
2.5mg/kg IV every 10 – 15 minutes (up to 10mg/kg). After the crisis, 1mg/kg IV every 4 – 6 hours for 24 hours.
Hyperventilate and treat acidosis, administer CaCl2, and give insulin with dextrose.
Pain, inflammation, pyrogenic effects, regulation of renal blood flow, increased gastric acid secretion, and increased protective mucus secretion in GIT.
Regional blood flow, area of the absorbing surface, gastric acid, intestinal motility, digestive enzymes, GIT bacteria, emesis, diseases of the GIT, diet, patient's compliance.
Activate phospholipase C
Rate of diffusion
Uncommon, genetically determined, dose-independent, mechanisms include receptor abnormality, immunological, and abnormal metabolism.
Conjugation of succinyl coenzyme A + glycine to form δ-amino-laevulinic acid, catalysed by amino-laevulinic acid synthetase.
IgG or IgM bind to cell surface antibodies, leading to complement activation via classical pathway, cell lysis, phagocytosis, and inflammation.
The advantages include rapid onset, avoidance of first-pass metabolism, and higher bioavailability due to venous drainage into the superior vena cava.
Anaphylaxis, malignant hyperthermia, porphyria, succinylcholine apnoea.
The potency of anaesthetic agents is related to their lipid solubility
Usually 100%
Autacoids with low molecular weight, synthesized from kininogens
Antigen presentation to T lymphocytes.
Depot preparations may be used, which is good for patients with poor compliance.
Succinylcholine and volatile anaesthetic agents
Large surface area (80m²), high regional blood flow, particle size (droplets < 1 micron reach alveoli, larger droplets reach only bronchioles), and method of administration.
It represents the relationship between drug concentration and drug effect in a single subject.
The middle third of the curve
α1-acid glycoprotein is an acute phase reactant that binds basic drugs with low capacity and more specific reaction.
Factors affecting protein binding include the affinity of the drug for the protein, the concentration of the binding proteins, the lipid solubility of the drug, ionisation, the number of available binding sites, and competition between the drug and endogenous compounds or other drugs for the same binding sites.
Ketamine, N2O, Xenon
Methadone, Tramadol
α, β, and γ
Histamine, Serotonin, Kinins, Prostaglandins
A receptor is a functional macromolecular component of cells to which one or more ligands may bind to initiate a specific response.
Enzyme induction and inhibition can change the oral bioavailability of drugs with high hepatic extraction ratio.
At any given dose of drug A, more of drug B is required to maintain a constant effect.
Use cooled IV fluids, surface cooling, and peritoneal lavage with cooled fluids.
Bronchodilation, increased H+ secretion from gastric parietal cells, increased heart rate, increased myocardial contractility, coronary vasodilation, peripheral vasodilation, increased capillary permeability
In the liver
A measure of the amount of drug that is required to produce a maximal effect.
Monoamine neurotransmitter
ABG, FBC, U&E, CK, coagulation profile, and myoglobin levels.
Non-microsomal enzymes; synthesized in the liver and RBCs
Barbiturates, Etomidate, Ketamine, Clonidine, Ketorolac, Diclofenac, Phenytoin, Erythromycin.
K_D represents the drug concentration at which 50% of the receptors are occupied and is a measure of affinity.
Slightly prolonged response to Sch (10 – 20 minutes)
Esmolol
Each vial contains 20 mg dantrolene sodium, 3 g mannitol, and is an orange powder.
Thickness of the diffusion membrane
Pulmonary endothelium contains enzymes that may metabolize some drugs such as lignocaine, fentanyl, propofol, and catecholamines.
On the sarcoplasmic reticulum
To mediate the release of Ca²⁺ from the sarcoplasmic reticulum
Contact dermatitis.
LD50
A drug that binds to and activates a receptor to produce a response
A drug that binds to and activates a receptor to produce a submaximal response
The orifice of the receptor is negatively charged, preventing anions from passing. Na+ influx is the most important.
An amino acid and major inhibitory neurotransmitter in the brain. Glutamate is converted to GABA + CO2 (catalysed by glutamate decarboxylase).
Pentameric structure (typically 2 α, 2 β, and 1 γ subunits). Altered by virtually all general anaesthetic agents except for ketamine and xenon.
No IA (IA = 0).
Guanine nucleotides (GDP and GTP)
Enzyme induction and the development of physiological compensatory mechanisms.
Reservoir patch (membrane-controlled system), matrix patch, adhesive polymer, patient-controlled transdermal system (utilizes iontophoresis, delivers fixed drug boluses).
Smooth muscle contraction, release of prostacyclin (PGI2) and NO from endothelial cells, decreased AVN conduction, coronary vasoconstriction, peripheral vasodilation, increased capillary permeability
The extraction ratio (ER) is the fraction of drug removed from the systemic circulation by an organ (typically the liver) during each pass through that organ.
Common, not genetically determined, dose-dependent, action due to the primary or secondary pharmacology of a drug.
Amiodarone and lignocaine.
CYP2D6
Heart block caused by β-blockers.
It dissociates from the βγ complex
Solubility
Hydrolyses ester bonds and is involved in organ-independent elimination
5HT3 (ligand-gated) and 5HT1, 2, 4, 5, 6, 7 (GPCRs)
Confirm with an in vitro caffeine and halothane contraction test.
By ethyl alcohol
Plasma α2-globulins
Dibucaine number 80
Diffusion
The movement of drug molecules down their concentration gradient without requiring interaction with carrier proteins.
Release of cytokines involves activation of macrophages and tissue damage, requiring 24 hours to reach maximal effect.
The movement of drug molecules down their concentration gradient with the help of carrier proteins.
Graded dose-response curve
The x-axis is logarithmic
A steeper curve indicates higher potency
Pentameric structure with 2 α subunits, 1 β subunit, 1 δ subunit, and 1 ε subunit (adult form) or 1 γ subunit (embryonic form)
Pregnancy, severe liver failure, renal failure, cardiac failure, malignancy, malnutrition, burns, thyrotoxicosis, after plasmapheresis, oral contraceptive pill, anticholinesterases, ketamine, metoclopramide, ester LAs.
The dibucaine number represents the percentage of inhibition of plasma cholinesterase.
A dibucaine number close to 80 indicates a normal enzyme concentration, while a lower number may indicate severe liver disease.
Convenient, good compliance, alternative route of administration, no pain, avoids 1st-pass metabolism, no large variations in plasma concentrations, lower incidence of side effects.
As the dose of drug A is increased, less of drug B is required to maintain a constant effect.
Examples include demethylation (diazepam), dehalogenation (volatiles), and hydroxylation (midazolam).
Liver disease can increase the oral bioavailability of drugs with high hepatic extraction ratio due to reduced first-pass metabolism.
A measure of the maximal response achievable by a drug once it is bound to its receptor.
Bronchodilation, vasodilation, and platelet anti-aggregation.
Dependence is a physical and/or psychological state associated with withdrawal symptoms when drug administration is abruptly ceased.
Autosomal dominant
8 – 16 hours
The concentration of a drug required to induce 50% of a maximal response.
Bronchospasm caused by β-blockers.
To determine susceptibility to malignant hyperthermia with high sensitivity and acceptable specificity.
Molecular weight
Remifentanil and atracurium
Serum sickness.
Autosomal dominant
It can cause general anaesthesia
Age, obesity, pregnancy
Can result in slow and fast acetylators, and conditions like succinylcholine apnoea
Cimetidine and omeprazole
Decrease in receptor density and structural changes in receptor morphology
Bound fraction and unbound fraction
A drug that binds to and activates a receptor to produce a maximal response
A drug that binds to a receptor to produce an effect in the opposite direction to that of the endogenous agonist for the same receptor
First-pass metabolism
GIT, lungs, vascular endothelium
Actions dependent on physicochemical properties include osmotic activity, acid-base activity, chelation, oxidation, and reduction.
GTN is highly extracted by the liver, resulting in negligible bioavailability when administered orally
Fractional IA (0 < IA < +1).
GPCRs (G-protein coupled receptors)
At any given dose of drug A, less of drug B is required to maintain a constant effect.
By E_max, the drug concentration at which a maximal effect is achieved.
Synthesis and release of histamine
Vasoconstriction and platelet aggregation.
The disadvantages include emesis, drug destruction by digestive enzymes and gastric acid, metabolism by GIT bacteria, and usually having the lowest bioavailability.
In the CNS and PNS
Usual (normal) allele, Atypical (dibucaine-resistant) allele, Silent (absent) allele, Fluoride-resistant allele
Deposition of antigen-antibody complexes in target tissues, leading to complement activation.
Propofol, N2O, Midazolam, Sch, NDMRs, Morphine, Fentanyl, Alfentanil.
Positive allosteric modulation
Painful, risk of local abscess, local hematoma, inadvertent IV administration, decreased regional blood flow, delayed absorption, slower onset leading to delayed effect, risk of toxic levels if further dose is given once perfusion is restored.
Glycine
Propofol, etomidate, barbiturates, and halogenated volatiles
Chloride ion channel opening in the absence of GABA
Pre-synaptic (e.g., baclofen)
Ligand-gated chloride channel
Retina
Dorsal horn of spinal cord and brain
In the myocardium
Acidic and neutral drugs
Mg²⁺
Ca²⁺ influx
A drug that binds to an allosteric site on the receptor and produces a conformational change that prevents receptor activation by the agonist. The antagonism is not reversible by increasing the dose of the agonist.
LD50 is close to ED50, narrow safety margin, usually require plasma concentration monitoring
TI = LD50 / ED50
Degree of systemic absorption through the GIT, degree of first-pass metabolism, hepatic enzyme activity, hepatic blood flow, drug uptake by hepatocytes
Mechanisms of drug action on receptors include alteration of ionic permeability, G-protein coupled receptors, receptors acting as enzymes, and regulation of gene transcription.
Drugs can inhibit enzymes (reversibly or irreversibly) or activate them.
The morphine PO:IV conversion ratio is 3:1
Absorption, distribution, metabolism, excretion.
Decarboxylation of histidine
Stimulate adenylate cyclase
Cross-tolerance refers to a reduced response to a drug due to tolerance developed to a different drug.
85%
Plasma, Brain, Liver, Kidneys
Bioavailability is calculated as the fraction absorbed multiplied by (1 - ER).
The theoretical volume into which a drug would need to be distributed following its administration to produce a desired plasma concentration.
Maintain urine output greater than 2 ml/kg/h.
CYP2E1
The dose of a drug required to produce a response in 50% of the population to whom it is administered.
Adenylate cyclase and Phospholipase C
Normal response to Sch
Difficult diffusion across cell membranes
Reverse it
Greatly prolonged response to Sch (4 – 8 hours)
Desulfuration is a chemical reaction involving the removal of sulfur from a molecule. An example is thiopental.
Glycine receptors
Etomidate
The desensitisation of receptors that are repeatedly exposed to an agonist
Barbiturates and phenytoin
It can impair the liver's ability to metabolize drugs, leading to altered drug efficacy and toxicity.
A drug whose antagonistic effect cannot be reversed by a higher concentration of the agonist. Both potency and efficacy are decreased.
The dose at which 50% of the population responds to the drug.
Oral bioavailability
By comparing the area under the curve (AUC) of identical bolus doses given IV and PO on separate occasions
A measure of the ability of a drug to produce an effect once it is bound to its receptor.
They become sensitized and degranulate, releasing inflammatory mediators.
The loading dose is used to get close to a steady state (desired plasma concentration) more quickly. LD = Vd x C.
Oxidation, which includes removal of electrons from molecules, is the main Phase I reaction. It is P450 driven.
Excretion is the removal of drugs from the body, while elimination is the removal of drugs from the plasma.
IA < 0.
Inhibit adenylate cyclase
Decreased duration and intensity of analgesia, euphoria, respiratory depression, and less tolerance to constipation and miosis.
12 hours
Bronchospasm and induction of labour.
The advantages of the oral route of drug administration include being cheap, convenient, and causing no pain on administration.
Vd = dose / C, where C is the plasma concentration of the drug.
Sch, Mivacurium, Ester LAs
Affinity is a measure of the degree of attraction between a drug and its receptor.
Drugs absorbed from the distal rectum avoid first-pass metabolism, while drugs absorbed from the proximal rectum undergo first-pass metabolism. This route can have local and/or systemic effects, variable pH, small surface area of absorption, and potential for local mucosal irritation.
Membrane hyperpolarisation
1:5000 – 1:50,000
They are involved in O2 transport (Hb, myoglobin) and the electron transport chain (cytochromes).
Antagonist at the α/γ interface
Ryanodine receptor mutations on chromosome 19
pKa of drug and pH of solution
At pH below their pKa
Phase II reactions involve the conjugation of the parent drug with endogenous substances, increasing water solubility. Examples include glucuronidation (morphine, propofol), sulphation (BDZs, propofol), acetylation (hydralazine), and methylation (catecholamines).
The Cytochrome P450 enzyme superfamily is named after the wavelength (nm) of their maximal absorption of light when in reduced form and combined with carbon monoxide.
Cytochrome P450 enzymes are located in the smooth endoplasmic reticulum of hepatocytes, gut mucosa, lungs, kidneys, and brain.
Prolonged treatment of asthma with β-adrenergic agonist leading to tachyphylaxis due to decreased receptor density
Increased receptor sensitivity after chronic deprivation of agonist either by denervation or chronic administration of antagonist
Increase in receptor density and improved communication between receptor and enzyme
Latex allergy.
Ephedrine causing depletion of noradrenaline stores
Decrease in receptor density and structural changes in receptor morphology
Secondary management steps for anaphylaxis include administering antihistamines (H1 and H2 antagonists), steroids, bronchodilators, and considering bicarbonate, glucagon, vasopressin, and serum mast cell tryptase.
The net effect is more than the sum of the individual effects.
It crosses the placenta into the foetus and some of it is converted into the ionised fraction, which does not cross back into the mother
The Cytochrome P450 enzyme superfamily is classified into families (e.g., CYP1, CYP2), subfamilies (e.g., CYP1A, CYP1B), and isoforms (e.g., CYP1A1, CYP1A2).
Only the unbound fraction
The reverse process of endocytosis.
The three major types of reactions to latex are irritant contact dermatitis, immediate hypersensitivity reaction (Type I), and delayed hypersensitivity reaction (Type IV).
Initial management steps for anaphylaxis include stopping administration of the offending agent, calling for help, checking ABC, administering 100% O2, adrenaline IM/IV, and IVF.
Interactions that involve physical or chemical changes, such as precipitation or chelation.
The net effect is equal to the sum of the individual effects.
The movement of drug molecules against their concentration gradient using energy derived directly from the breakdown of ATP or other high-energy phosphate compounds.
Latex is derived from the Brazilian rubber tree (Hevea brasiliensis).
A drug that binds to an allosteric site on the receptor and produces a conformational change that increases or decreases the affinity of the receptor for the endogenous agonist.
It decreases the affinity of the receptor for the endogenous agonist.
The binding of a drug to metal ions, which can decrease absorption.
One drug increases the effect of the other, and one of the drugs has no independent action on its own.
Smoking can induce certain liver enzymes, altering the metabolism of various drugs.
In the brain
Glycine
Partial depolarisation of the cell membrane
Nitric oxide production, activation and production of 2nd messengers, activation of enzymatic processes
When the net effect is less than the sum of the individual effects.
The process where vesicles containing drug molecules are moved across the cell membrane into the cell by invagination.
Routes of exposure to latex include airborne, IV, and mucosa.
It increases the affinity of the receptor for the endogenous agonist.
A drug that has agonist properties at one receptor type and antagonist properties at another receptor type.
NDMRs + nicotinic acetylcholine receptors at the NMJ.
Tetracyclines + Ca2+ leading to decreased absorption.
Enzyme induction and inhibition.
Combination of NSAID and opioid.
Repeated administration of a drug is associated with a rapid decrease in the response to that drug
Increased doses of a drug are required to produce the same effect
Stop the trigger, declare an emergency, and call for help
The second gas effect.
Interactions that affect the drug's effect on the body, such as antagonism, summation, potentiation, and synergism.
Increased heart rate, masseter spasm after succinylcholine, increased ETCO₂, and cardiac arrhythmias
Myoglobinuria, raised serum CK, coagulopathy, and cardiac arrest
Central sensitisation, learning and memory, cerebral ischaemic damage
Receptors that exist where maximal effect is achieved when only a fraction of the receptors are occupied.
Thiopental + Sch leading to precipitation.
Combination of two different opioids.
Rapid rise in temperature, sweating, progressive metabolic and respiratory acidosis, hyperkalaemia, and generalized muscle rigidity
Risk factors for latex allergy include occupational exposure to latex (health care professionals, workers in the rubber industry), children with spina bifida and urogenital abnormalities, history of atopy, and cross-reactivity with some foods (banana, avocado, kiwi).
Pentazocine is an agonist at κ receptors and antagonist at μ receptors.
Interactions that affect the absorption, distribution, metabolism, or excretion of a drug.
Drugs that compete for the same active transport system.
BDZs are positive allosteric modulators at the GABA_A receptors.
Drugs that compete for the same protein binding sites.
Aminoglycosides increase competitive neuromuscular blockade.
