Pharmacology - First Aid Flashcards
Enzyme Kinetics:
Michaelis-Menten Kinetics
- Km is inversely related to the affinity of the enzyme for its substrate.
- Vmax is directly proportional to the enzyme concentration.
- Most enzymatic reactions follow a hyperbolic curve (ie, Michaelis-Menten kinetics); however, enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (eg, hemoglobin).
Enzyme Kinetics:
Lineweaver-Burk Plot
- ↑ y-intercept, ↓ Vmax
- The further to the right the x-intercept (ie. closer to zero), the greater the Km and the lower the affinity.
- Competitive inhibitors cross each other, whereas noncompetitive inhibitors do not.
- Kompetitive inhibitors increase Km.
Inhibitors
Inhibitors:
- resembles substrate
- overcome by ↑ [S]
- binda active site
- no effect on Vmax
- ↑ Km
- ↓ potency
Reversible Competitive Inhibitors
Inhibitors:
- resembles substrate
- not overcome by ↑ [S]
- binds active site
- ↓ Vmax
- no effect on Km
- ↓ efficacy
Irreversible Competitive Inhibitors
Inhibitors:
- does not resemble substrate
- not overcome by ↑ [S]
- does not bind active site
- ↓ Vmax
- no effect on Km
- ↓ efficacy
Noncompetitive Inhibitors
Pharmacokinetics:
fraction of administered drug reaching systemi circulation unchanged
Bioavailability
Bioavailability of IV Dose
F = 100%
Bioavailability of Oral Dose
F typically < 100% due to incomplete absorption and first-pass metabolism
Pharmacokinetics:
theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration
Volume of Distribution (Vd)
- Apparent Vd of plasma protein–bound drugs can be altered by liver and kidney disease (↓ protein binding, ↑ Vd).
- Drugs may distribute in more than one compartment.
Pharmacokinetics:
- the volume of plasma cleared of drug per unit time
- may be impaired with defects in cardiac, hepatic, or renal function
Clearance (CL)
Pharmacokinetics:
the time required to change the amount of drug in the body by 1⁄2 during elimination
Half-Life (t1/2)
- In first-order kinetics, a drug infused at a constant rate takes 4–5 half-lives to reach steady state.
- It takes 3.3 half-lives to reach 90% of the steady-state level.
Dosage Calculations
- In renal or liver disease, maintenance dose ↓ and loading dose is usually unchanged.
- Time to steady state depends primarily on t1/2 and is independent of dose and dosing frequency.
Types of Drug Interactions:
- effect of substance A and B together is equal to the sum of their individual effects
- Aspirin
- Acetaminophen
Additive
Types of Drug Interactions:
- presence of substance A is required for the full effects of substance B
- Cortisol on catecholamine responsiveness
Permissive
Types of Drug Interactions:
- effect of substance A and B together is greater than the sum of their individual effects
- Clopidogrel with Aspirin
Synergistic
Types of Drug Interactions:
- acute decrease in response to a drug after initial/repeated administration
- Nitrates
- Niacin
- Phenylephrine
- LSD
- MDMA
Tachyphylactic
Receptor Binding
Receptor Binding:
- shifts curve right (↓ potency), no change in efficacy
- can be overcome by ↑ the concentration of agonist substrate
- Diazepam (agonist) + Flumazenil (antagonist) on GABA receptor
Competitive Antagonist
Receptor Binding:
- shifts curve down (↓ efficacy)
- cannot be overcome by ↑ agonist substrate concentration
- Norepinephrine (agonist) + Phenoxybenzamine (antagonist) on α-receptors
Noncompetitive Antagonist
Receptor Binding:
- acts at same site as full agonist, but with lower maximal effect (↓ efficacy)
- potency is an independent variable
- Morphine (full agonist) vs. Buprenorphine (_____ agonist) at opioid μ-receptors
Partial Agonist
Elimination of Drugs:
- rate of elimination is constant regardless of Cp (ie. constant amount of drug eliminated per unit time)
- Cp ↓ linearly with time
- capacity-limited elimination
- Phenytoin
- Ethanol
- Aspirin (at high or toxic concentrations)
Zero-Order Elimination
Elimination of Drugs:
- rate is directly proportional to the drug concentration (ie. constant fraction of drug eliminated per unit time)
- Cp ↓ exponentially with time
- applies to most drugs
- flow-dependent elimination
First-Order Elimination
Urine pH and Drug Elimination:
trapped in urine and cleared quickly
Ionized Species
Urine pH and Drug Elimination:
can be reabsorbed
Neutral Forms
Urine pH and Drug Elimination:
Weak Acids
- Trapped in basic environments.
- Treat overdose with sodium bicarbonate to alkalinize urine.
- Examples:
- Phenobarbital
- Methotrexate
- Aspirin (Salicylates)
Urine pH and Drug Elimination:
Weak Bases
- Trapped in acidic environments.
- Treat overdose with ammonium chloride to acidify urine.
- TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channelblocking activity of TCAs, but not for accelerating drug elimination.
- Examples:
- TCAs
- Amphetamines
Drug Metabolism:
- Reduction, Oxidation, Hydrolysis with cytochrome P-450 usually yield slightly polar, water-soluble metabolites (often still active).
- Geriatric patients lose this phase first.
Phase I
R-OH:
- Reduction
- Oxidation
- Hydrolysis
Drug Metabolism:
- Conjugation (Methylation, Glucuronidation, Acetylation, Sulfation) usually yields very polar, inactive metabolites (renally excreted).
- Geriatric patients have more of this phase.
- Patients who are slow acetylators have ↑ side effects from certain drugs because of ↓ rate of metabolism.
Phase II
Geriatric patients have More GAS (phase II).
- Methylation
- Glucuronidation
- Acetylation
- Sulfation
_____ is the maximal effect a drug can produce.
Efficacy
- Represented by the y-value (Vmax). ↑ y-value = ↑ Vmax = ↑ efficacy.
- Unrelated to potency (ie. efficacious drugs can have high or low potency).
- Partial agonists have less efficacy than full agonists.
_____ is the amount of drug needed for a given effect.
Potency
- Represented by the x-value (EC50).
- Left shifting = ↓ EC50 = ↑ potency = ↓ drug needed.
- Unrelated to efficacy (ie. potent drugs can have high or low efficacy).
_____ is the measurement of drug safety.
Therapeutic Index
- TITE: Therapeutic Index = TD50 / ED50
- Safer drugs have higher TI values.
- Drugs with lower TI values frequently require monitoring (eg. Warfarin, Theophylline, Digoxin, Lithium; Warning! These Drugs are Lethal!).
- LD50 (lethal median dose) often replaces TD50 in animal studies.
_____ is the dosage range that can safely and effectively treat disease.
Therapeutic Window
Central and Peripheral Nervous System
- Pelvic splanchnic nerves and CNs III, VII, IX and X are part of the parasympathetic nervous system.
- Adrenal medulla is directly innervated by preganglionic sympathetic fibers.
- Sweat glands are part of the sympathetic pathway but are innervated by cholinergic fibers.
Acetylcholine Receptors:
ligand-gated Na+/K+ channels
Nicotinic
- NN (found in autonomic ganglia, adrenal medulla)
- NM (found in neuromuscular junction of skeletal muscle)
Acetylcholine Receptors:
G-protein–coupled receptors that usually act through 2nd messengers
Muscarinic
- M1–5 found in heart, smooth muscle, brain, exocrine glands, and on sweat glands (cholinergic sympathetic).
G-Protein–Linked Second Messengers:
- Sympathetic
- G-Protein: q
- ↑ vascular smooth muscle contraction
- ↑ pupillary dilator muscle contraction (mydriasis)
- ↑ intestinal and bladder sphincter muscle contraction
α1
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Sympathetic
- G-Protein: i
- ↓ sympathetic (adrenergic) outflow
- ↓ insulin release
- ↓ lipolysis
- ↑ platelet aggregation
- ↓ aqueous humor production
α2
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Sympathetic
- G-Protein: s
- ↑ heart rate
- ↑ contractility (one heart)
- ↑ renin release
- ↑ lipolysis
β1
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Sympathetic
- G-Protein: s
- vasodilation
- bronchodilation (two lungs)
- ↑ lipolysis
- ↑ insulin release
- ↑ glycogenolysis
- ↓ uterine tone (tocolysis)
- ↑ aqueous humor production
- ↑ cellular K+ uptake
β2
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Sympathetic
- G-Protein: s
- ↑ lipolysis
- ↑ thermogenesis in skeletal muscle
- ↑ bladder relaxation
β3
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Parasympathetic
- G-Protein: q
- mediates higher cognitive functions
- stimulates enteric nervous system
M1
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Parasympathetic
- G-Protein: i
- ↓ heart rate and contractility of atria
M2
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Parasympathetic
- G-Protein: q
- ↑ exocrine gland secretions (eg. lacrimal, sweat, salivary, gastric acid)
- ↑ gut peristalsis
- ↑ bladder contraction
- bronchoconstriction
- ↑ pupillary sphincter muscle contraction (miosis)
- ciliary muscle contraction (accommodation)
- ↑ insulin release
M3
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Dopamine
- G-Protein: s
- relaxes renal vascular smooth muscle
- activates direct pathway of striatum
D1
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Dopamine
- G-Protein: i
- modulates transmitter release, especially in brain
- inhibits indirect pathway of striatum
D2
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Histamine
- G-Protein: q
- ↑ nasal and bronchial mucus production
- ↑ vascular permeability
- bronchoconstriction
- pruritus
- pain
H1
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Histamine
- G-Protein: s
- ↑ gastric acid secretion
H2
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Vasopressin
- G-Protein: q
- ↑ vascular smooth muscle contraction
V1
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers:
- Vasopressin
- G-Protein: s
- ↑ H2O permeability and reabsorption via upregulating aquaporin-2 in collecting twobules (tubules) of kidney
V2
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
G-Protein–Linked Second Messengers
Autonomic Drugs
- Release of norepinephrine from a sympathetic nerve ending is modulated by NE itself, acting on presynaptic α2-autoreceptors → negative feedback.
- Amphetamines use the NE transporter (NET) to enter the presynaptic terminal, where they utilize the vesicular monoamine transporter (VMAT) to enter neurosecretory vesicles. This displaces NE from the vesicles.
- Once NE reaches a concentration threshold within the presynaptic terminal, the action of NET is reversed, and NE is expelled into the synaptic cleft, contributing to the characteristics and effects of ↑ NE observed in patients taking amphetamines.
When using cholinomimetic agents, you should watch out for _____ in susceptible patients.
- exacerbation of COPD
- asthma
- peptic ulcers
Cholinomimetic Agents:
- direct agonist
- activates bowel and bladder smooth muscle
- resistant to AChE
- no nicotinic activity
- postoperative ileus
- neurogenic ileus
- urinary retention
Bethanechol
“Bethany, call (bethanechol) me to activate your bowels and bladder.”
Cholinomimetic Agents:
- direct agonist
- carbon copy of acetylcholine (but resistant to AChE)
- constricts pupil
- relieves intraocular pressure in open-angle glaucoma
Carbachol
Carbachol = carbon copy of acetylcholine
Cholinomimetic Agents:
- direct agonist
- stimulates muscarinic receptors in airway when inhaled
- challenge test for diagnosis of asthma
Methacholine
Cholinomimetic Agents:
- direct agonist
- contracts ciliary muscle of eye (open-angle glaucoma) and pupillary sphincter (closed-angle glaucoma)
- resistant to AChE
- can cross blood-brain barrier (tertiary amine)
- potent stimulator of sweat, tears, and saliva
- xerostomia (Sjögren syndrome)
Pilocarpine
“You cry, drool, and sweat on your ‘pilow.’ ”
Cholinomimetic Agents:
- indirect agonist (anticholinesterase)
- ↑ ACh
- Alzheimer disease
- Donepezil
- Rivastigmine
- Galantamine
Dona & Riva dances at the gala.
Cholinomimetic Agents:
- indirect agonist (anticholinesterase)
- ↑ ACh
- historically used to diagnose myasthenia gravis
- replaced by anti-AChR Ab (anti-acetylcholine receptor antibody) test
Edrophonium
Cholinomimetic Agents:
- indirect agonist (anticholinesterase)
- ↑ ACh
- postoperative and neurogenic ileus and urinary retention
- myasthenia gravis
- reversal of neuromuscular junction blockade (postoperative)
Neostigmine
Neo CNS = No CNS penetration (quaternary amine).
Cholinomimetic Agents:
- indirect agonist (anticholinesterase)
- ↑ ACh
- antidote for anticholinergic toxicity
- atropine overdose
Physostigmine
Phreely (freely) crosses blood-brain barrier → CNS (tertiary amine).
Cholinomimetic Agents:
- indirect agonist (anticholinesterase)
- ↑ ACh
- ↑ muscle strength
- myasthenia gravis (long acting)
- does not penetrate CNS (quaternary amine)
Pyridostigmine
_____ is often due to organophosphates, such as parathion, that irreversibly inhibit AChE. Organophosphates are often components of insecticides; poisoning usually seen in farmers.
Cholinesterase Inhibitor Poisoning
Symptoms of Cholinesterase Inhibitor Poisoning
DUMBBELSS
- Diarrhea
- Urination
- Miosis
- Bronchospasm
- Bradycardia
- Emesis
- Lacrimation
- Sweating
- Salivation
*may lead to respiratory failure if untreated
_____ is the antidote for cholinesterase inhibitor poisoning.
Atropine (competitive inhibitor) + Pralidoxime (regenerates AChE if given early)
Muscarinic Antagonists:
- eye
- mydriasis
- cycloplegia
- Atropine
- Homatropine
- Tropicamide
Muscarinic Antagonists:
- CNS
- Parkinson disease
- acute dystonia
- Benztropine
- Trihexyphenidyl
Park my Benz.
Muscarinic Antagonists:
- GI
- respiratory
- Parenteral: preoperative use to reduce airway secretions
- Oral: drooling, peptic ulcer
Glycopyrrolate
Muscarinic Antagonists:
- GI
- antispasmodics for irritable bowel syndrome
- Hyoscyamine
- Dicyclomine
Muscarinic Antagonists:
- respiratory
- COPD
- asthma
- Ipratropium
- Tiotropium
Muscarinic Antagonists:
- genitourinary
- reduce bladder spasms
- urge urinary incontinence (overactive bladder)
- Oxybutynin
- Solifenacin
- Tolterodine
Muscarinic Antagonists:
- CNS
- motion sickness
Scopolamine
_____ is a muscarinic antagonist used to treat bradycardia and for ophthalmic applications. It blocks DUMBBeLSS in cholinesterase inhibitor poisoning. Does not block excitation of skeletal muscle and CNS (mediated by nicotinic receptors).
Atropine
Atropine Effects:
Eye
- ↑ pupil dilation
- cycloplegia
Atropine Effects:
Airway
- bronchodilation
- ↓ secretions
Atropine Effects:
Stomach
↓ acid secretion
Atropine Effects:
Gut
↓ motility
Atropine Effects:
Bladder
↓ urgency in cystitis
Adverse Effects of Atropine
- *Hot** as a hare
- *Dry** as a bone
- *Red** as a beet
- *Blind** as a bat
- *Mad** as a hatter
- *Full** as a flask
- ↑ body temperature (due to ↓ sweating)
- rapid pulse
- dry mouth
- dry, flushed skin
- cycloplegia
- constipation
- disorientation
- Can cause acute angle-closure glaucoma in elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants.
_____ causes gardener’s pupil (mydriasis due to plant alkaloids).
Jimson weed (Datura)
Direct Sympathomimetics:
- β2 > β1
- acute asthma
- COPD
Albuterol
Direct Sympathomimetics:
- β2 > β1
- long-term asthma
- COPD
Salmeterol
Direct Sympathomimetics:
- β2 > β1
- bronchospasm in asthma
- tocolysis
Terbutaline
Direct Sympathomimetics:
- β1 > β2, α
- heart failure
- cardiogenic shock (inotropic > chronotropic)
- cardiac stress testing
Dobutamine
Direct Sympathomimetics:
- D1 = D2 > β > α
- unstable bradycardia
- heart failure
- shock
- inotropic and chronotropic effects at lower doses due to β effects
- vasoconstriction at high doses due to α effects
Dopamine
Direct Sympathomimetics:
- β > α
- anaphylaxis
- asthma
- open-angle glaucoma
- α effects predominate at high doses
- significantly stronger effect at β2-receptor than norepinephrine
Epinephrine
Direct Sympathomimetics:
- D1
- postoperative hypertension
- hypertensive crisis
- vasodilator (coronary, peripheral, renal, and splanchnic)
- promotes natriuresis
- can cause hypotension and tachycardia
Fenoldopam
Direct Sympathomimetics:
- β1 = β2
- electrophysiologic evaluation of tachyarrhythmias
- can worsen ischemia
- has negligible α effect
Isoproterenol
Direct Sympathomimetics:
- α1
- autonomic insufficiency and postural hypotension
- may exacerbate supine hypertension
Midodrine
Direct Sympathomimetics:
- β3
- urinary urge incontinence or overactive bladder
Mirabegron
Direct Sympathomimetics:
- α1 > α2 > β1
- hypotension
- septic shock
Norepinephrine
Direct Sympathomimetics:
- α1 > α2
- hypotension (vasoconstrictor)
- ocular procedures (mydriatic)
- rhinitis (decongestant)
- ischemic priapism
Phenylephrine
Indirect Sympathomimetics:
- indirect general agonist
- reuptake inhibitor
- releases stored catecholamines
Amphetamine
Indirect Sympathomimetics:
- indirect general agonist
- reuptake inhibitor
- causes vasoconstriction and local anesthesia
- caution when giving β-blockers if intoxication is suspected (can lead to unopposed α1 activation, activation → extreme hypertension, coronary vasospasm).
Cocaine
Indirect Sympathomimetics:
- indirect general agonist
- releases stored catecholamines
- nasal decongestion (pseudoephedrine)
- urinary incontinence
- hypotension
Ephedrine
Norepinephrine vs. Isoproterenol
- NE ↑ systolic and diastolic pressures as a result of α1-mediated vasoconstriction → ↑ mean arterial pressure → reflex bradycardia.
- Isoproterenol (rarely used) has little α effect but causes β2-mediated vasodilation, resulting in ↓mean arterial pressure and ↑ heart rate through β1 and reflex activity.
Sympatholytics (α2-agonists):
- Applications:
- hypertensive urgency (limited situations)
- ADHD
- Tourette syndrome
- symptom control in opioid withdrawal
- Adverse Effects:
- CNS depression
- bradycardia
- hypotension
- respiratory depression
- miosis
- rebound
- hypertension with abrupt cessation
- Clonidine
- Guanfacine
Sympatholytics (α2-agonists):
- Applications:
- hypertension in pregnancy
- Adverse Effects:
- direct Coombs ⊕ hemolysis
- drug-induced lupus
α-methyldopa
Sympatholytics (α2-agonists):
- Applications:
- relief of spasticity
- Adverse Effects:
- hypotension
- weakness
- xerostomia
Tizanidine
α-Blockers:
- nonselective
- irreversible
- Applications:
- pheochromocytoma (used preoperatively) to prevent catecholamine (hypertensive) crisis
- Adverse Effects:
- orthostatic hypotension
- reflex tachycardia
Phenoxybenzamine
α-Blockers:
- nonselective
- reversible
- Applications:
- give to patients on MAO inhibitors who eat tyramine-containing foods and for severe cocaine-induced hypertension (2nd line)
- Adverse Effects:
- orthostatic hypotension
- reflex tachycardia
Phentolamine
α-Blockers:
- α1 selective
- Applications:
- urinary symptoms of BPH
- PTSD (prazosin)
- hypertension (except tamsulosin)
- Adverse Effects:
- 1st-dose orthostatic hypotension, dizziness, headache
- Prazosin
- Terazosin
- Doxazosin
- Tamsulosin
α-Blockers:
- α2 selective
- Applications:
- depression
- Adverse Effects:
- sedation
- ↑ serum cholesterol
- ↑ appetite
Mirtazapine
Effects of α-Blocker on BP Responses to Epinephrine and Phenylephrine
- Epinephrine response exhibits reversal of mean arterial pressure from a net increase (the α response) to a net decrease (the β2 response). properties).
- Phenylephrine response is suppressed but not reversedbecause it is a “pure” α-agonist (lacks β-agonist properties).
β-Blockers
- Acebutolol
- Atenolol
- Betaxolol
- Bisoprolol
- Carvedilol
- Esmolol
- Labetalol
- Metoprolol
- Nadolol
- Nebivolol
- Pindolol
- Propranolol
- Timolol
β-Blocker Applications:
↓ heart rate and contractility, resulting in ↓ O2 consumption
Angina Pectoris
β-Blocker Applications:
↓ production of aqueous humor
Glaucoma
- Timolol
β-Blocker Applications:
↓ mortality
- Heart Failure
- Bisoprolol
- Carvedilol
- Metoprolol
- Myocardial Infarction
β-Blocker Applications:
- ↓ cardiac output
- ↓ renin secretion (due to β1-receptor blockade on JGA cells)
Hypertension
β-Blocker Applications:
- symptom control (↓ heart rate, ↓ tremor),
- thyroid storm
Hyperthyroidism
- Propranolol
β-Blocker Applications:
↓ heart rate → ↑ filling time, relieving obstruction
Hypertrophic Cardiomyopathy
β-Blocker Applications:
↓ AV conduction velocity (class II antiarrhythmic)
Supraventricular Tachycardia
- Metoprolol
- Esmolol
β-Blocker Applications:
- ↓ hepatic venous pressure gradient
- portal hypertension (prophylactic use)
Variceal Bleeding
- Nadolol
- Propranolol
- Carvedilol
Adverse Effects of β-Blockers
- erectile dysfunction
- cardiovascular (bradycardia, AV block, HF)
- CNS (seizures, sleep alterations)
- dyslipidemia (metoprolol)
- asthma/COPD exacerbations
- use with caution in cocaine users due to risk of unopposed α-adrenergic receptor agonist activity
β-Blocker Selectivity:
β1-Selective Antagonists (β1 > β2)
- Acebutolol (partial agonist)
- Atenolol
- Betaxolol
- Bisoprolol
- Esmolol
- Metoprolol
Selective antagonists mostly go from A to M (β1 with 1st half of alphabet)
β-Blocker Selectivity:
Nonselective Antagonists (β1 = β2)
- Nadolol
- Pindolol (partial agonist)
- Propranolol
- Timolol
Nonselective antagonists mostly go from N to Z (β2 with 2nd half of alphabet)
β-Blocker Selectivity:
Nonselective α- and β-Antagonists
- Carvedilol
- Labetalol
Nonselective α- and β-antagonists have modified suffixes (instead of “-olol”).
_____ combines cardiac-selective β1‑adrenergic blockade with stimulation of β3‑receptors (activate nitric oxide synthase in the vasculature and ↓ SVR).
Nebivolol
Nebivolol increases NO.
Ingested Seafood Toxins
- Histamine (Scombroid poisoning)—Histamine release
- Tetrodotoxin—Total block of Na+ channels
- Ciguatoxin—opening of Na+ channels to Cause depolarization
Ingested Seafood Toxins:
- spoiled dark-meat fish such as tuna, mahimahi, mackerel, and bonito
- bacterial histidine decarboxylase converts histidine to histamine
- frequently misdiagnosed as fish allergy
- mimics anaphylaxis: acute burning sensation of mouth, flushing of face, erythema, urticaria, itching
- may progress to bronchospasm, angioedema, and hypotension
- treated with antihistamines, Albuterol and Epinephrine if needed
Histamine (Scombroid poisoning)
Ingested Seafood Toxins:
- pufferfish
- highly potent toxin
- binds fast voltage-gated Na+ channels in cardiac/nerve tissue, preventing depolarization
- nausea, diarrhea, paresthesias, weakness, dizziness, loss of reflexes
- supportive therapy
Tetrodotoxin
Ingested Seafood Toxins:
- reef fish such as barracuda, snapper, and moray eel
- opens Na+ channels, causing depolarization
- nausea, vomiting, diarrhea; perioral numbness
- reversal of hot and cold sensations
- bradycardia, heart block, hypotension
- supportive therapy
Ciguatoxin
_____ is a widely used criteria developed to reduce potentially inappropriate prescribing and harmful polypharmacy in the geriatric population. Includes > 50 medications that should be avoided in elderly patients due to ↓ efficacy and/or ↑ risk of adverse events.
Beers Criteria
- α-Blockers (↑ risk of hypotension)
- Anticholinergics, Antidepressants, Antihistamines, Opioids (↑ risk of delirium, sedation, falls, constipation, urinary retention)
- Benzodiazepines (↑ risk of delirium, sedation, falls)
- NSAIDs (↑ risk of GI bleeding, especially with concomitant anticoagulation)
- PPIs (↑ risk of C. difficile infection)
Antidotes:
Acetaminophen
N-acetylcysteine (replenishes glutathione)
Antidotes:
- AChE Inhibitors
- Organophosphates
Atropine > Pralidoxime
Antidotes:
- Antimuscarinic agents
- Anticholinergic agents
- Physostigmine
- control hyperthermia
Antidotes:
Arsenic
- Dimercaprol
- Succimer
Antidotes:
Benzodiazepines
Flumazenil
Antidotes:
β-blockers
- Atropine
- Glucagon
Antidotes:
Carbon Monoxide
- 100% O2
- Hyperbaric O2
Antidotes:
Copper
- Penicillamine (copper penny)
- Trientine
Antidotes:
Cyanide
- Nitrite
- Thiosulfate
- Hydroxocobalamin
Antidotes:
Digitalis (Digoxin)
Anti-dig Fab fragments
Antidotes:
Heparin
Protamine Sulfate
Antidotes:
Iron
- Deferoxamine
- Deferasirox
- Deferiprone
Antidotes:
Lead
- EDTA
- Dimercaprol
- Succimer
- Penicillamine
Antidotes:
Mercury
- Dimercaprol
- Succimer
Antidotes:
- Methanol
- Ethylene Glycol (antifreeze)
- Fomepizole > Ethanol
- Dialysis
Antidotes:
Methemoglobin
- Methylene Blue
- Vitamin C (reducing agent)
Antidotes:
Opioids
Naloxone
Antidotes:
Salicylates
- NaHCO3 (alkalinize urine)
- dialysis
Antidotes:
TCAs
NaHCO3 (stabilizes cardiac cell membrane)
Antidotes:
Warfarin
- Vitamin K (delayed effect)
- fresh frozen plasma (immediate)
Drug Reactions—Cardiovascular:
coronary vasospasm
CASE
- Cocaine
- Amphetamines
- Sumatriptan
- Ergot Alkaloids
Drug Reactions—Cardiovascular:
cutaneous flushing
Flushed from VANCEN (dancing):
- Vancomycin
- Adenosine
- Niacin
- Ca2+ Channel Blockers
- Echinocandins
- Nitrates
Drug Reactions—Cardiovascular:
dilated cardiomyopathy
Anthracyclines
- Doxorubicin
- Daunorubicin
*prevented with Dexrazoxane
Drug Reactions—Cardiovascular:
torsades de pointes
Prolong QT Interval (ABCDE):
- antiArrhythmics (class IA, III)
- antiBiotics (eg. macrolides)
- anti“C”ychotics (eg. haloperidol)
- antiDepressants (eg. TCAs)
- antiEmetics (eg. ondansetron)
Drug Reactions—Endocrine/Reproductive:
adrenocortical insufficiency
HPA suppression 2° to glucocorticoid withdrawal
Drug Reactions—Endocrine/Reproductive:
diabetes insipidus
- Lithium
- Demeclocycline
Drug Reactions—Endocrine/Reproductive:
hot flashes
SERMs
- Tamoxifen
- Clomiphene
- Raloxifene
Drug Reactions—Endocrine/Reproductive:
hyperglycemia
The People Need Hard Candies:
- Tacrolimus
- Protease Inhibitors
- Niacin
- HCTZ
- Corticosteroids
Drug Reactions—Endocrine/Reproductive:
hyperprolactinemia
- Typical Antipsychotics (eg. haloperidol)
- Atypical Antipsychotics (eg. quetiapine)
- Metoclopramide
- Methyldopa
*presents with hypogonadism (eg. infertility, amenorrhea, erectile dysfunction) and galactorrhea (more common in men)
Drug Reactions—Endocrine/Reproductive:
hyperthyroidism
- Lithium
- Amiodarone
Drug Reactions—Endocrine/Reproductive:
hypothyroidism
I AM SUddenly Lethargic:
- AMiodarone
- SUlfonamides
- Lithium
Drug Reactions—Endocrine/Reproductive:
SIADH
Can’t Concentrate Serum Sodium:
- Carbamazepine
- Cyclophosphamide
- SSRIs
Drug Reactions—Gastrointestinal:
- acute cholestatic hepatitis
- jaundice
Macrolides (eg. Erythromycin)
Drug Reactions—Gastrointestinal:
diarrhea
- Acamprosate
- Antidiabetic Agents (eg. Acarbose, Metformin, Pramlintide)
- Colchicine
- Cholinesterase Inhibitors
- Lipid-Lowering Agents (eg. Ezetimibe, Orlistat)
- Macrolides (eg. Erythromycin)
- Quinidine
- SSRIs
Drug Reactions—Gastrointestinal:
focal to massive hepatic necrosis
Liver “HAVAc”
- Halothane
- Amanita phalloides (death cap mushroom)
- Valproic Acid
- Acetaminophen
Drug Reactions—Gastrointestinal:
hepatitis
- Rifampin
- Isoniazid
- Pyrazinamide
- Statins
- Fibrates
Drug Reactions—Gastrointestinal:
pancreatitis
Drugs Causing A Violent Abdominal Distress:
- Didanosine
- Corticosteroids
- Alcohol
- Valproic Acid
- Azathioprine
- Diuretics (Furosemide, HCTZ)
Drug Reactions—Gastrointestinal:
pill-induced esophagitis
- Bisphosphonates
- Ferrous Sulfate
- NSAIDs
- Potassium Chloride
- Tetracyclines
*caustic effect minimized with upright posture and adequate water ingestion
Drug Reactions—Gastrointestinal:
pseudomembranous colitis
- Ampicillin
- Cephalosporins
- Clindamycin
- Fluoroquinolones
*sntibiotics predispose to superinfection by resistant C. difficile
Drug Reactions—Hematologic:
agranulocytosis
Can Cause Pretty Major Collapse of Granulocytes:
- Clozapine
- Carbamazepine
- Propylthiouracil
- Methimazole
- Colchicine
- Ganciclovir
Drug Reactions—Hematologic:
aplastic anemia
Can’t Make New Blood Cells Properly:
- Carbamazepine
- Methimazole
- NSAIDs
- Benzene
- Chloramphenicol
- Propylthiouracil
Drug Reactions—Hematologic:
direct Coombs positive hemolytic anemia
P. Diddy Coombs:
- Penicillin
- MethylDopa
- Cephalosporins
Drug Reactions—Hematologic:
drug reaction with eosinophilia and systemic symptoms (DRESS)
- Allopurinol
- Anticonvulsants
- Antibiotics
- Sulfa Drugs
_____ is a potentially fatal delayed hypersensitivity reaction. Latency period (2–8 weeks) followed by fever, morbilliform skin rash, and frequent multiorgan involvement. Treatment: withdrawal of offending drug, corticosteroids.
DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)
Drug Reactions—Hematologic:
gray baby syndrome
Chloramphenicol
Drug Reactions—Hematologic:
hemolysis in G6PD deficiency
Hemolysis IS D PAIN:
- Isoniazid
- Sulfonamides
- Dapsone
- Primaquine
- Aspirin
- Ibuprofen
- Nitrofurantoin
Drug Reactions—Hematologic:
megaloblastic anemia
You’re having a mega blast with PMS.
- Hydroxyurea
- Phenytoin
- Methotrexate
- Sulfa Drugs
Drug Reactions—Hematologic:
thrombocytopenia
Help! Very Low platelets!
- Heparin
- Vancomycin
- Linezolid
Drug Reactions—Hematologic:
thrombotic complications
- Combined Oral Contraceptives
- Hormone Replacement Therapy
- SERMs (eg. Tamoxifen, Raloxifene, Clomiphene)
*estrogen-mediated side effect
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
drug-induced lupus
Having lupus is Mega “SHIPP-E”
- Methyldopa
- Sulfa Drugs
- Hydralazine
- Isoniazid
- Procainamide
- Phenytoin
- Etanercept
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
fat redistribution
Fat PIG:
- Protease Inhibitors
- Glucocorticoids
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
gingival hyperplasia
Can Cause Puffy Gums
- Cyclosporine
- Ca2+ Channel Blockers
- Phenytoin
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
hyperuricemia (gout)
Painful Tophi and Feet Need Care.
- Pyrazinamide
- Thiazides
- Furosemide
- Niacin
- Cyclosporine
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
myopathy
- Statins
- Fibrates
- Niacin
- Colchicine
- Daptomycin
- Hydroxychloroquine
- Interferon-α
- Penicillamine
- Glucocorticoids
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
osteoporosis
- Corticosteroids
- Depot Medroxyprogesterone Acetate
- GnRH Agonists
- Aromatase Inhibitors
- Anticonvulsants
- Heparin
- PPIs
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
photosensitivity
SAT For photo:
- Sulfonamides
- Amiodarone
- Tetracyclines
- 5-FU
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
rash (Stevens-Johnson syndrome)
Steven Johnson has epileptic allergy to sulfa drugs and penicillin.
- Anti-Epileptic drugs (Lamotrigine)
- Allopurinol
- Sulfa Drugs
- Penicillin
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
teeth discoloration
Tetracyclines
Teethracyclines
Drug Reactions—Musculoskeletal/Skin/Connective Tissue:
tendon and cartilage damage
Fluoroquinolones
Drug Reactions—Neurologic:
cinchonism
- Quinidine
- Quinine
*can present with tinnitus, hearing/vision loss, psychosis, and cognitive impairment
Drug Reactions—Neurologic:
Parkinson-like syndrome
cogwheel rigidity of ARM:
- Antipsychotics
- Reserpine
- Metoclopramide
Drug Reactions—Neurologic:
peripheral neuropathy
- Phenytoin
- Vincristine
Drug Reactions—Neurologic:
pseudotumor cerebri
- Growth Hormones
- Tetracyclines
- Vitamin A
Drug Reactions—Neurologic:
seizures
With seizures, I BITE my tongue.
- Isoniazid (vitamin B6 deficiency)
- Bupropion
- Imipenem/Cilastatin
- Tramadol
- Enflurane
Drug Reactions—Neurologic:
tardive dyskinesia
- Antipsychotics
- Metoclopramide
Drug Reactions—Neurologic:
visual disturbance
These Drugs Irritate Very Precious Eyes:
- Topiramate (blurred vision/diplopia, haloes)
- Digoxin (yellow-tinged vision)
- Isoniazid (optic neuropathy/color vision changes)
- Vigabatrin (bilateral visual field defects)
- PDE-5 inhibitors (blue-tinged vision)
- Ethambutol (color vision changes)
Drug Reactions—Renal/Genitourinary:
Fanconi syndrome
- Cisplatin
- Ifosfamide
- expired Tetracyclines
- Tenofovir
Drug Reactions—Renal/Genitourinary:
hemorrhagic cystitis
- Cyclophosphamide
- Ifosfamide
*prevent by coadministering with Mesna
Drug Reactions—Renal/Genitourinary:
interstitial nephritis
- Penicillins
- Furosemide
- NSAIDs
- Proton Pump Inhibitors
- Sulfa Drugs
Drug Reactions—Respiratory:
dry cough
ACE Inhibitors
Drug Reactions—Respiratory:
pulmonary fibrosis
My Nose Cannot Breathe Bad Air.
- Methotrexate
- Nitrofurantoin
- Carmustine
- Bleomycin
- Busulfan
- Amiodarone
Drug Reactions—Multiorgan:
antimuscarinic
- Atropine
- TCAs
- H1-Blockers
- Antipsychotics
Drug Reactions—Multiorgan:
Disulfiram-like reaction
Sorry Pals, Can’t Go Mingle.
- 1st-Generation Sulfonylureas
- Procarbazine
- Cephalosporins
- Griseofulvin
- Metronidazole
Drug Reactions—Multiorgan:
nephrotoxicity/ototoxicity
Listen And Pee Very TERriBly:
- Loop Diuretics
- Aminoglycosides
- CisPlatin
- Vancomycin
- AmphoTERicin B
*Cisplatin toxicity may respond to amifostine
Drugs affecting pupil size:
↑ pupil size (mydriasis)
- Anticholinergics (atropine, TCA, tropicamide, scopolamine, antihistamines)
- Drugs of Abuse (amphetamines, cocaine, LSD)
- Sympathomimetics
Drugs affecting pupil size:
↓ pupil size (miosis)
- Antipsychotics (haloperidol, risperidone, olanzapine)
- Drugs of Abuse (eg. heroin/opioids)
- Parasympathomimetics (pilocarpine)
- Organophosphates
Cytochrome P-450 Inducers (+)
Most chronic alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs.
- Modafinil
- Chronic Alcohol Use
- St. John’s Wort
- Phenytoin
- Phenobarbital
- Nevirapine
- Rifampin
- Griseofulvin
- Carbamazepine
Cytochrome P-450 Substrates
Always Think When Outdoors:
- Anti-Epileptics
- Theophylline
- Warfarin
- OCPs
Cytochrome P-450 Inhibitors (–)
SICKFACES.COM (when I Am drinking grapefruit juice):
- Sodium Valproate
- Isoniazid
- Cimetidine
- Ketoconazole
- Fluconazole
- Acute Alcohol Abuse
- Chloramphenicol
- Erythromycin/Clarithromycin
- Sulfonamides
- Ciprofloxacin
- Omeprazole
- Metronidazole
- Amiodarone
- Grapefruit Juice
Sulfa Drugs
Scary Sulfa Pharm FACTS:
- Sulfonamide Antibiotics
- Sulfasalazine
- Probenecid
- Furosemide
- Acetazolamide
- Celecoxib
- Thiazides
- Sulfonylureas
Patients with sulfa allergies may develop _____. Symptoms range from mild to life threatening.
- fever
- urinary tract infection
- Stevens-Johnson syndrome
- hemolytic anemia
- thrombocytopenia
- agranulocytosis
- acute interstitial nephritis
- urticaria (hives)
Antimicrobials:
ergosterol synthesis inhibitor
-azole
Ketoconazole
Antimicrobials:
antiparasitic/antihelminthic
-bendazole
Mebendazole
Antimicrobials:
transpeptidase (penicillin-binding protein)
-cillin
Ampicillin
Antimicrobials:
protein synthesis inhibitor
-cycline
Tetracycline
Antimicrobials:
neuraminidase inhibitor
-ivir
Oseltamivir
Antimicrobials:
protease inhibitor
-navir
Ritonavir
Antimicrobials:
DNA polymerase inhibitor
-ovir
Acyclovir
Antimicrobials:
macrolide antibiotic
-thromycin
Azithromycin
CNS Drugs:
inhalational general anesthetic
-ane
Halothane
CNS Drugs:
typical antipsychotic
-azine
Thioridazine
CNS Drugs:
barbiturate
-barbital
Phenobarbital
CNS Drugs:
local anesthetic
-caine
Lidocaine
CNS Drugs:
TCA
- -ipramine
- -triptyline
Imipramine
Amitriptyline
CNS Drugs:
5-HT1B/1D Agonist
-triptan
Sumatriptan
CNS Drugs:
benzodiazepine
- -zepam
- -zolam
Diazepam
Alprazolam
Autonomic Drugs:
cholinergic agonist
-chol
Bethanechol
Carbachol
Autonomic Drugs:
nondepolarizing paralytics
- -curium
- -curonium
Atracurium
Vecuronium
Autonomic Drugs:
β-blocker
-olol
Propranolol
Autonomic Drugs:
AChE inhibitor
-stigmine
Neostigmine
Autonomic Drugs:
β2-agonist
-terol
Albuterol
Autonomic Drugs:
α1-antagonist
-zosin
Prazosin
Cardiovascular Drugs:
PDE-5 inhibitor
-afil
Sildenafil
Cardiovascular Drugs:
dihydropyridine Ca2+ channel blocker
-dipine
Amlodipine
Cardiovascular Drugs:
ACE inhibitor
-pril
Captopril
Cardiovascular Drugs:
angiotensin-II receptor blocker
-sartan
Losartan
Cardiovascular Drugs:
direct factor Xa inhibitor
-xaban
Apixaban
Edoxaban
Rivaroxaban
Drugs:
bisphosphonate
-dronate
Alendronate
Drugs:
DPP-4 inhibitors
-gliptin
Sitagliptin
Drugs:
PPAR-γ activator
-glitazone
Rosiglitazone
Drugs:
calcineurin inhibitor
-limus
Everolimus
Tacrolimus
Drugs:
proton pump inhibitor
-prazole
Omeprazole
Drugs:
prostaglandin analog
-prost
Latanoprost
Drugs:
endothelin receptor antagonist
-sentan
Bosentan
Drugs:
H2-antagonist
-tidine
Cimetidine
Drugs:
pituitary hormone
-tropin
Somatotropin
Monoclonal Antibodies:
chimeric human-mouse monoclonal Ab
-ximab
Rituximab
Monoclonal Antibodies:
humanized mouse monoclonal Ab
-zumab
Bevacizumab
Monoclonal Antibodies:
human monoclonal Ab
-mumab
Ipilimumab
Small Molecule Inhibitors:
tyrosine kinase inhibitor
-tinib
Imatinib
Small Molecule Inhibitors:
proteasome inhibitor
-zomib
Bortezomib
Small Molecule Inhibitors:
cyclin-dependent kinase inhibitor
-ciclib
Palbociclib
Receptor Fusion Proteins:
TNF-α antagonist
-cept
Etanercept
Interleukin Receptor Modulators:
IL-2 agonist/analog
-leukin
Aldesleukin
Interleukin Receptor Modulators:
interleukin receptor antagonist
-kinra
Anakinra
