Pharmacokinetics and Autonomic Drugs Flashcards
What is Bioavailability
Bioavailability (F) = % drug administered that reaches systemic circulation unchanged
In what instances is Bioavailability (F) 100%
IV administration, and in kids: interosseous
What is Volume of Distribution (Vd)
Vd = amount of drug in body / [drug] in plasma
What can change Volume of Distribution (Vd)?
kidney and liver diseases can change the Vd of protein bound drugs
What is the equation for half-life?
t1/2 = 0.7xVd/CL
What is clearance (Cl)
Clearance = rate of elimination / [drug] in plasma Clearance = Vd x Ke (Ke= elimination constant)
What is Loading Dose
Loading Dose = Cp x Vd/F where Cp = target [drug] in plasma
What is Maintenance Dose and what causes it to decrease
Maintenance Dose = Cp x Cl/F where Cp = target [drug] in plasma
Decreases in liver and kidney diseases because of decreased clearance
What is Steady State?
Depends on half-life of drug.
Most drugs require 4-5 half-lifes to reach steady state.
Not effected by frequency or amount of dosing
What is the difference between Zero and First order elimination?
0 order = constant amount is eliminated
eg: start 100, 80, 60, 40, 20, 0
1st order = constant fraction is eliminated
eg: start 100, 50, 25, 12.5, 6.25 etc
Which drugs are Zero order?
“Zero PEAs for me”
Phenytoin, Ethanol, Aspirin
What are weak acid drugs, where do they get trapped and how do you treat overdose?
Aspirin, Methotrexate, Phenobarbital
Trapped in basic environments
Use bicarbonate to treat overdose by ionizing, and trapping in urine
What are weak base drugs, where do they get trapped and how do you treat overdose?
Amphetamines
Trapped in acidic environments
Use ammonium chloride to treat overdose and trap in urine
What are Phase 1 types of drug metabolism? Which enzyme do they require? What do they yield? What occurs in Geriatric patients?
Reduction, Oxidation, Hydrolysis
Require cytochrome P450
Yield slightly polar, water-soluble, usually active metabolites
Phase 1 is lost first in geriatric patients
What are Phase 2 types of drug metabolism? What do they yield?
Glucuronidation, Acetylation, Conjugation
Yield very polar, inactive metabolites which are renally excreted
What occurs in slow acetylators?
increased side effects of drugs due to slower metabolism
Receptor a1: what g-protein class, and what are its functions
Gq,
Increase contraction of: vascular SmM, pupillary dilator muscle (mydriasis), intestinal and bladder sphincter muscle
Receptor a2: what g-protein class, and what are its functions
Gi,
Decrease sympathetic outflow, insulin release, lipolysis
increase platelet aggregation
Receptor b1: what g-protein class, and what are its functions
Gs,
Increase heart rate, contractility, renin release, lipolysis
Receptor b2: what g-protein class, and what are its functions
Gs,
Vasodilation, bronchodilation
Increased heart rate, contractility, lipolysis, insulin release, aqueous humor production
Decreased uterine tone, ciliary muscle relaxation
Receptor M1: what g-protein class, and what are its functions
Gq,
CNS, enteric nervous system
Receptor M2: what g-protein class, and what are its functions
Gi,
decrease heart rate, contractility of atri
Receptor M3: what g-protein class, and what are its functions
Gq,
Increased exocrine gland secretion (lacrimal, gastric etc), gut peristalsis, contraction of bladder, bronchioles, pupillary sphincter muscle (miosis), ciliary muscle (acommodation)
Receptor D1: what g-protein class, and what are its functions
Gs,
relaxes renal vascular SmM
Receptor D2: what g-protein class, and what are its functions
Gi,
Modulates transmitter release, especially in brain
Receptor H1: what g-protein class, and what are its functions
Gq,
increased nasal, bronchial mucus production, contraction of bronchioles, puritis, pain
Receptor H2: what g-protein class, and what are its functions
Gs,
Increased gastric acid secretion
Receptor V1: what g-protein class, and what are its functions
Gq,
Increased vascular SmM contraction
Receptor V2: what g-protein class, and what are its functions
Gs,
Increased H2O permeability, reabsorption in collecting tubules of kidney
Hemicholinium: Site of action,
Inhibits choline reuptake on presynaptic cholinergic neuron
Vesamicol: Site of action
Cholinergic neuron: Inhibits intracellular transportation of Acetyl-CoA and Choline via ChAT into secretory vessicle for assembly into ACh
Botulinum: site of action
Cholinergic neuron: Inhibits release of ACh into synaptic cleft
Metyrosine: Site of action
Noradrenergic neuron: inhibits conversion of tyrosine into dopa, therefore decreasing production of dopamine and NE
Reserpine: Site and mechanism of action
Noradrenergic neuron: irreversibly blocks VMAT (vesiclular monoamine transporter) so that NE, 5HT3, and Dopamine cannot enter secretory vesicles for exocytosis. They are degraded by MAO and COMT in the cytoplasm, and [monoamine] in the synapse is depeated, leading to depression
Guanethidine, Bretylium: site of action
inhibit release of NE into synapse
Amphetamine: site of action
increases release of NE into synase
Cocaine, TCAs, Amphetamines
inhibit reuptake of NE into presynaptic neuron
Bethanechol: Direct or Indirect agonist? Clinical application? Action?
Direct agonist (cholinomimetic)
Application: Postoperative ileus, neurogenic ileus (constipation), urinary retention
Action: (+) bowel and bladder SmM, resistant to AChE
“BETHANy, CHOL me if you want to activate your bowels and bladder”
Carbachol: Direct or Indirect agonist? Clinical application? Action?
Direct agonist (cholinomimetic) Application: glaucoma, pupillary contraction, relief of intraocular pressure Action: "CARBon copy of ACh"
Pilocarpine: Direct or Indirect agonist? Clinical application? Action?
Direct agonist (cholinomimetic)
Application: open-angle and closed-angle glaucoma
Action: potent stimulator of sweat, tears, saliva.
Contracts ciliary muscle of eye for open-angle, and pupillary sphinter for closed angle. resistant to AChE
“Cry, Drool, Sweat on your PILOw”
Methacholine: Direct or Indirect agonist? Clinical application? Action?
Direct agonist (cholinomimetic)
Application: challenge test for asthma
Action: (+) M receptors in airway
Neostigmine: Direct or Indirect agonist? Clinical application? Action?
Indirect Agonist (anti-AChE) Application: same as Bethanechol (postoperative neurogenic ileus and urinary retention) + myasthenia gravis, reversal of neuromuscular junction blockade (postop) Action: increase endogenous ACh, "Neo CNS = No CNS penetration"
Pyridostigmine: Direct or Indirect agonist? Clinical application? Action?
Indirect agonist (anti-AChE) Application: Myasthenia gravis (long acting), does not penetrate CNS Action: same as neostigmine. Increase endogenous ACh so increase strength "pyRIDostiGMine gets RID of Myasthenia Gravis"
Edrophonium: Direct or Indirect agonist? Clinical application? Action?
Indirect agonist (anti-AChE) Application: diagnosis of myasthenia gravis (extremely short acting) Action: increases endogenous ACh
Physostigmine: Direct or Indirect agonist? Clinical application? Action?
Indirect agonist (anti-AChE) **do not confuse with pyridostigmine for myasthenia Application: Anticholinergic toxicity ( x BBB into CNS) Action: increase endogenous ACh **FOR ATROPINE OD "Physostigmine Phyxes atropine OD"
Donepezil: Direct or Indirect agonist? Clinical application? Action?
Indirect agonist (Anti-AChE) Application: Alzheimer's Action: increase endogenous ACh
Cholinesterase Inhibitor Poisoning: Causes, effects, antidote
Causes: organophosphates (Parathion) found in insecticides, which irreversibly (-) AChE
Effects: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal musc and cns, Lacrimation, Sweating, Salivation
Antidote: atropine + pralidoxime (regenerates AChE)
Atropine, Homatropine, Tropicamide: Drug type, Organ system, Application
Muscarinic antagonist
Eye
Produce mydriasis and cycloplegia
Benztropine: Drug type, Organ system, Application
Muscarinic antagonist
CNS
Parkinsons “Park my Benz”
Scopolamine: Drug type, Organ system, Application
Muscarinic antagonist
CNS + auditory nerve
Motion sickness
Ipratropium, Tiotropium: Drug type, Organ system, Application
Muscarinic antagonist
Respiratory
COPD, Asthma “IPRAy i can breathe soon”
Oxybutynin: Drug type, Organ system, Application
Muscarinic antagonist
Genitourinary
Reduce urgency in mild cystitis and reduce bladder spasms
Glycopyrrolate: Drug type, Organ system, Application
Muscarinic antagonist
GI, Respiratory
Parenteral: preop for reducing airway secretions; Oral: drooling, peptic ulcer
Atropine: Drug type, Main Use, Action, Toxicity, Side Effects
Muscarinic antagonist
Main use: bradycardia and ophthalmic
Action:
- increase pupil dilation and cycloplegia,
- decrease airway secretions, stomach acid secretions, gut motility, bladder urgency in cystitis
- BLOCKS DUMBBeLSS but not excitation of CNS and SkM because that is mediated by nicotinic receptors
Toxicity:
- increase body temp (since decr sweating), rapid pulse, dry mouth, dry flushed skin, cycloplegia, constipation, disorientation (“hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter”)
- acute-CLOSURE glaucoma in elderly due to mydriasis, urinary retention in men w/ BPH, and hyperthermia in infants
- Jimson Weed
Epinephrine: Drug type, Receptor affinity, Application
Direct Sympathomimetic
b > a, no affinity for D1
Application: anaplylaxis, open angle glaucoma, asthma, hypotension
Norepinephrine: Drug type, Receptor affinity, Application, Cardiovascular effects
Direct Sympathomimetic
a > b1, no affinity for b2 or D1
Application: hypotension (but decrease renal perfusion)
CV effects: a1 mediated increase in systolic and diastolic pressures due to vasoconstriction, incr MAP, leading to bradycardia
Isoproterenol: Drug type, Receptor affinity, Application, Cardiovascular effects
Direct Sympathomimetic
b1 and 2, no affinity for a or D
Application: Torsade de pointes (tachycardia decreases QT interval), bradyarrhythmias (but may worsen ischemia)
CV effects: b2 mediated vasodilation leading to decreased MAP and increased HR through b1 reflex
Dopamine: Drug type, Receptor affinity, Application
Direct Sympathomimetic
D1 at low dose, b1 and b2 at medium dose, a1 and a2 at high dose
Application: Shock (renal perfusion), HF, inotropic and chronotropic
Dobutamine: Drug type, Receptor affinity, Application
Direct Sympathomimetic
b1»_space; b2 or a1, a2
Application: HF, cardiac stress testing, inotropic and chronotropic
Phenylephrine: Drug type, Receptor affinity, Application
Direct Sympathomimetic
a1 > a2, no affinity for b or D1
Application: hypotension (vasoconstriction), occular procedures (mydriatic), rhinitis (decongestant)
Metaproterenol, Albuterol, salmeterol, terbutaline: Drug type, Receptor affinity, Application
Direct Sympathomimetic
b2»_space; b1, no affinity for a or D1
Application:
- metaproterenol and albuterol for acute asthma
- salmeterol for long-term asthma or COPD
- terbutaline to reduce premature uterine contractions
Ritodrine: Drug type, Receptor affinity, Application
Direct Sympathomimetic
b2 only
Application: reduces premature uterine contractions
Amphetamine: Drug type, Mechanism, Application
Indirect Sympathomimetic
releases stored catecholamines
Application: narcolepsy, obesity, ADD
Ephedrine: Drug type, Mechanism, Application
Indirect Sympathomimetic
releases stored catecholamines
Application: Nasal decongestion, urinary incontinence, hypotension
Cocaine: Drug type, Mechanism, Application, Contraindication
Indirect Sympathomimetic
Reuptake inhibitor
Application: Vasoconstriction and local anesthesia
Contraindication: Never give b-blocker if cocaine intoxication is suspected (lead to unopposed a1 activation, extreme htn)
Clonidine, a-methyldopa: Drug type, Mechanism, Application
Sympathoplegics
Centrally acting a2-agonist, decrease central sympathetic outflow
Application: HTN (especially w/ renal dz)
Phenoxybenzamine: Drug type, Application, Toxicity
Irreversible Nonselective a-blocker
Pheochromocytoma – used before removing tumor to irreversibly block a-receptors since it won’t be overcome by the high levels of released catecholamines
Toxicity: orthostatic hypotension, reflex tachycardia
Phentolamine: Drug type, Application
Reversible Nonselective a-blocker
For patients on MAO inhibitors who eat tyramine-containing foods (red wine, cheese, fish)
(Praz/Teraz/Doxaz/Tamsul)-osin: Drug type, Application, Toxicity
“-osin” = a1-selective blocker
For htn, urinary retention in BPH
Toxicity: first dose orthostatic hypotension, dizziness, headache
Mirtazapine: Drug type, Application, Toxicity
a2-selective blocker
For depression
Toxicity: sedation, increased serum cholesterol and appetite
(Acebut-, betax-, esm-, aten-, metopr-, propran-, tim-, pind-, labet-)-olol: Drug type, Application and effect, Toxicity, Use with caution in…
b-blockers
Angina pectoris – decrease HR, contractility, so less O2 consumption
MI – decrease mortality
Hypertension – decrease CO and renin secretion (because JGA cell b1 blockade!!)
CHF – slow progression of chronic failure
Toxicity: impotence, exacerbation of asthma, cardiovasc (bradycardia, AV block, CHF), CNS (seizures, sedation, sleep alterations)
Caution in diabetics because b2 receptors increase insulin release so inhibiting b will decrease insulin leading to hyperglycemia
b-blockers for SVT
metoprolol, esmolol (class II antiarrhythmic)
b-blocker for glaucoma
timolol
decrease secretion of aqueous humor
Name the b1-selective antagonists, and use
Acebutalol (partial agonist), Betaxolol, Esmolol (short acting), Atenolol, Metoprolol
Advantageous in pts w/ comorbid pulmonary disease
Name the non-selective b antagonists
Propranolol, Timolol, Nadolol, Pindolol
Name the non-selective vasodilatory a- and b-antagonists
Carvedilol, Labetalol
Name the partial b-agonists
Pindolol and acebutalol
Partial Agonist Pindolol Acebutalol (PAPA)
note: pindolol is also non-selective antagonist, and acebutalol is b1 selective antagonist)
