Pharmacology Flashcards
Pharmacokinetics
The effect of the body on the drug
ADME:
Absorption, distribution, metabolism, excretion
Pharmacodynamics
The effects of the drug on the body
Includes drug efficacy, drug potency, drug toxicity
Bioavailability (F)
Fraction of administered drug that reaches systemic circulation unchanged
For an IV dose, F = 100%
Orally F typically <100% due to incomplete absorption and first-pass metabolism
Volume of distribution Vd
Theoretical volume occupied by the total absorbed drug amount at the plasma concentration measured
Vd = amount of drug / plasma drug concentration
Low Vd: drug in Vd
Medium Vd: drug in ECF
High Vd: drug in all tissues including fat
Half life T1/2
Time required to change the amount of drug in the body by 1/2 during elimination
Property of ONLY first-order elimination
Drug infused at a constant rate takes 4-5 half lives to reach steady state
T1/2 = (0.693 x Vd) / Clearance (CL)
Clearance CL
The volume of plasma cleared of drug per unit time.
Clearance may be impaired with defects in cardiac, hepatic, or renal function
CL = rate of elimination / plasma drug concentration
Dosage calculation
Loading dose = (Cp (target concentration) x Vd ) / F
Maintenance dose = (Cp x CL x tau (dosage interval) ) / F
In renal or liver disease, maintenance dose decreases but loading dose is usually unchanged
Zero order elimination
Rate of elimination is constant regardless of drug concentration
Concentration decreases linearly w time
Ex: phenytoin, ethanol, aspirin
First order elimination
Rate of elimination is directly proportional to the drug concentration
Concentration decreases exponentially w time
Urine pH and drug elimination
Ionized species are trapped in urine and cleared quickly while neutral ones are often reabsorbed
Weak acids: aspirin, methotrexate, trapped in basic environment, add bicarb for overdose
Weak bases: amphetamines, trapped in acidic environment, add ammonium chloride for overdose
Drug metabolism
Phase I: reduction, oxidation, hydrolysis with cytochrome p450, usually yields slightly polar, water-soluble metabolites often still active
Phase II: conjugation (glucuronidation, acetylation, sulfation) usually yields very polar, inactive metabolites (renal excreted)
Geriatric patients often lose phase 1 before phase 2
Efficacy
Maximal effect a drug can produce
High efficacy drug classes are analgesic medications, antibiotics, antihistamines
Partial agonists often have less efficacy than full agonists
Potency
Amount of drug needed for a given effect
Increased potency usually means increased affinity for a certain receptor
Highly potent drugs include chemotherapeutic drugs, antihypertensives, and lipid lowering drugs
Competitive antagonist
No change in efficacy but decreases potency of original drug
Efficacy is overcomes by increasing the concentration of original agonist substrate
Noncompetitive antagonist/irreversible competitive antagonist
Decreases efficacy.
Cannot be overcome by increasing concentration of original agonist substrate
Partial agonist
Acts at the same site as full agonist, but with lower maximal efficacy.
Potency can vary compare to full agonist depending on concentration and type
Nicotinic Ach receptor
Ligand gated Na/K channels
Nn found in autonomic ganglia
Nm found in neuromuscular junction
Muscarinic Ach receptor
G protein coupled receptors that usually act through 2ndary messengers
5 subtypes: M1,2,3,45
Alpha1 receptor
Sympathetic
Increase vascular smooth muscle contraction
Increase pupillary dilator muscle contraction
Increase intestinal and blade sphincter muscle contraction
Alpha2 receptor
Sympathetic
Decrease sympathetic outflow
Decrease insulin release
Decrease lipolysis
Beta1 receptor
Sympathetic
Increase heart rate
Increase heart contractility
Increase renin release
Increase lipolysis
Beta2 receptor
Sympathetic
Vasodilation Bronchodilation Increase heart rate Increase heart contractility Increase insulin release Decrease uterine tone Increase aqueous humor production
M1
Parasympathetic
CNS
Enteric nervous system
M2
Parasympathetic
Decrease heart rate
Decrease contractility of atria
M3
Parasympathetic
Increase exocrine gland secretions
Increase gut peristalsis
Increase blade contraction
Increase pupillary sphincter muscle contraction
Ciliary muscle contraction for accomondation
D1
Dopamine
Relaxes renal vascular smooth muscle
D2
Dopamine
Modulates transmitter release, especially in brain
H1
Histamine
Increase nasal and bronchial mucus production
Increase vascular permeability
H2
Histamine
Increase gastric acid secretion
V1
Vasopressin
Increase vascular smooth muscle contraction
V2
Vasopressin
Increase water permeability and reabsorption in the collecting tubules of kidney
Bethanechol
Cholinergic agonist
Activates bowel and bladder smooth muscle, resistant to AChEsterase
For postoperative ileus, neurogenic ileus, and urinary retention
Carbachol
Cholinergic agonist
For glaucoma and relief of intraocular pressure
Pilocarpine
Cholinergic agonist
Resistant to AChE
Potent stimulator of sweat, tears, and saliva
Treatment for open angle and close angle glaucoma
Neostigmine
Anti-AChE
Increases ACh
For posteroperative and neurogenic ileus and urinary retention, myasthenia gravis
Pyridostigmine
Anti-AChE
Increase ACh
For myasthenia gravis, does not penetrate CNS
Physostigmine
Anti-AChE
Increase ACh
Penetrates CNS, treats anticholinergic toxicity (atropine overdose)
Donepzil, rivastigmine
Anti-AChE
Increase ACh
For Alzheimer disease
AChE inhibitor poisoning
Too much cholinergics
Often due to organophosphates, such as components of insecticides, that irreversibly inhibit AChE
DUMBBELSS: Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skeletal muscle and CNS Lacrimination Sweating Salivation
Antidote: atropine (competitive inhibitor) + pralidoxinme (regenerates AChE if used early)
Atropine
Muscarinic antagonist
Blocks DUMBBELSS
Also used to treat bradycardia
Toxicity: too much anticholinergic
hot as hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter
Can cause acute angle glaucoma in elderly
Benztropine
Muscarinic antagonist
Used to treat Parkinsons
Ipratropium
Muscarinic antagonist
Used to treat COPD and asthma
Oxybutynin
Muscarinic antagonist
Used to reduce urinary urgency
Glycopyrrolate
Muscarinic antagonist
Used to reduce airway secretions and prevent peptic ulcers
Epinephrine
Sympathomimetic
Beta > alpha
Treat anaphylaxis, open angle glaucoma, asthma, hypotension
Alpha effects become predominate effect at high dose
Norepinephrine
Sympathomimetic
Alpha1 > alpha2 > beta 1
Treat hypotension
Dopamine
Sympathomimetic
D1=D2 > beta > alpha
Treat unstable bradycardia, heart failure, shock
Dobutamine
Sympathomimetic
B1 > B2,alpha
Treat heart failure, for cardiac stress test
Phenylephrine
Sympathomimetic
A1 > A2
Treat hypotension, rhinitis (decongestant)
Albuterol, salmeterol
Sympathomimetic
B2 > B1
Asthma, COPD
Amphetamine
Indirect general sympathetic agonist, reuptake inhibitor, release stored catecholemines
Treat narcolepsy, ADHD
Ephedrine
Indirect general sympathetic agonist, release stored catecholemines
Treat nasal congestion, urinary incontinence, hypotension
Cocaine
Indirect general sympathetic agonist, reuptake inhibitor
NEVER give beta blocker if cocaine intoxication is suspected
Clonidine
Sympatholytic (alpha2 agonist)
Treat hypertenisve urgency, ADHD
Toxicity: CNS depression, bradycardia, hypotension, respiratory depression
Methyldopa
Sympatholytic (alpha2 agonist)
Treat hypertension in pregnancy (only one safe in pregnancy)
Toxicity: hemolytic anemia, SLE-like symptoms
Phenoxybenzamine
Alpha blocker, irreversible
Treat pheochromocytoma to prevent catechlolamine crisis
Phentolamine
Alpha blocker, reversible
Give to pts on MAO inhibitor if they eat tyramine-containing food
Prazosin, tamsulosin
Alpha 1 blocker
Treat urinary symptoms of BPH
Mirtazapine
Alpha 2 blocker
Treat depression
Beta blockers
Decrease heart rate/contractility, resulting in decreased O2 consumption –> angina
Decreases MI mortality
Decreases AV conduction velocity –> prevent SVT
Decrease cardiac output and renin secretion –> HTN
Decreases aqueous humor secretion –> glaucoma (timolol)
Toxicity: impotence, bradycardia, AV block, seizures, sedation
Avoid in cocaine users
B1 selective block: atenolol, metoprolol
Non selective alpha block: propanolol
Non selective alpha and beta block: labetalol, carvedilol
