Autonomic Flashcards
Pharmacokinetics
Effects of body on drug Absorption Distribution Metabolism Excretion
Pharmacodynamics
Effects of drug on body Receptor binding Drug efficacy Drug potency Toxicity
a1 receptors
Gq (phospholipase C)
Increase vascular smooth muscle contraction
Increase pupillary dilator muscle contraction (mydriasis)
Increase intestinal and bladder sphincter muscle contraction
a2 receptors
Gi (inhibitory; adenylyl cyclase)
Decrease sympathetic outflow
Decrease insulin release
Decrease lipolysis
Increase platelet aggregation
B1 receptors
Gs (excitatory; adenylyl cyclase)
Increase HR, contractility, renin release, and lipolysis
B2 receptors
Gs (excitatory; adenylyl cyclase)
Vasodilation, bronchodilation
Increase HR, contractility, lypolysis, insulin release, and aqueous humor production
Decrease uterine tone (tocolysis)
Ciliary muscle relaxation
M1
Gq (phospholipase C)
CNS
Enteric nervous system
M2
Gi (inhibitory; adenylyl cyclase)
Decrease HR and contractility of atria
M3
Gq (phopholipase C)
Increase exocrine gland secretions (lacrimal, salivary, gastric acid), gut peristalsis, bladder contraction, pupillary sphincter muscle contraction (miosis)
Bronchoconstriction
Ciliary muscle contraction (accommodation)
D1
Gs (adenylyl cyclase)
Relaxes renal vascular smooth muscle
D2
Gi (inhibitory; adenylyl cyclase)
Modulates transmitter release, especially in brain
H1
Gq (phospholipase C)
Increase nasal and bronchial mucus production Increase vascular permeability Contraction of bronchioles Pruritus Pain
H2
Gs (adenylyl cyclase)
Increase gastric acid secretion
V1
Gq (phospholipase C)
Increase vascular smooth muscle contraction
V2
Gs (adenylyl cyclase)
Increase H2O permeability and reabsorption in the collecting tubules of the kidney (V2 is found in the 2 kidneys)
Phospholipase C pathway (Gq)
Converts PIP2 –> DAG + IP3
DAG –> Protein kinase C
IP3 –> Increased [Ca2+] = smooth muscle contraction
H1, a1, V1
M1, M3
“HaVe 1 M&M”
Adenylyl cyclase pathway (Gs)
Converts ATP –> cAMP
cAMP activates protein kinase A = increases [Ca2+] in heart and inhibits myosin light-chain kinase in smooth muscle
B1, B2, D1
H2, V2
Adenylyl cyclase pathway (Gi)
INHIBITORY
Blocks conversion of ATP to cAMP, PKA, etc.
M2, a2, D2
“MAD 2’s”
Drugs blocking cholinergic synthesis
Hemicholinium
Vesamicol
Botulinum
AChE inhibitors
Drugs blocking noradrenergic synthesis
Metyrosine Reserpine Bretylium, guanethidine Amphetamine Cocaine, TCAs, amphetamines
Fraction of administered drug that reaches systemic circulation unchanged
Bioavailability (F)
Volume of distribution
Amount of drug in body/plasma drug concentration
Volume occupied by total absorbed drug amount at plasma concentration
Altered by liver and kidney disease
Low Vd
Blood (4-8 L)
Large/charged molecules; plasma protein bound
Medium Vd
ECF
Small hydrophilic molecules
High Vd
All tissues including fat
Small lipophilic molecules, especially if bound to tissue protein
Half life
T1/2 = (0.693 x Vd)/Cl
Property of first order elimination
A drug infused at a constant rate takes how long to reach steady state?
4-5 half lives
Clearance
Volume of plasma cleared of drug per unit time
Cl = rate of elimination of drug/plasma drug concentration Cl = Vd x Ke (elimination constant)
Impaired with cardiac, hepatic, or renal dysfunction
Loading dose
Loading dose = (Cp x Vd)/F
Cp = target plasma concentration at steady state
Maintenance dose
Maintenance dose = (Cp x Cl x dosage interval)/F
In renal or liver disease, maintenance dose decreases and loading dose is unchanged
Does time to steady state depend on dose and dosing frequency?
NO = time to steady state depends primarily on T1/2 and is independent of dose and dosing frequency
Zero order elimination
Rate of elimination constant = constant AMOUNT eliminated per unit time
“Capacity-limited”
Decreases linearly with time
Zero order elimination examples (3)
Phenytoin
Ethanol
Aspirin (at high or toxic concentrations)
“PEA” = round like 0 in zero order
First order elimination
Rate of elimination directly proportional to drug concentration = constant FRACTION eliminated per unit time
Plasma concentration decreases EXPONENTIALLY with time
“Flow dependent”
Weak acids (3) Overdose treatment?
Phenobarbital Methotrexate Aspirin Trapped in basic environments Treat overdose with bicarbonte!!!
Weak bases (1) Overdose treatment?
Amphetamines
Trapped in acidic environment
Treat overdose with ammonium chloride
Phase I metabolism
Reduction
Oxidation
Hydrolysis with CYP450
Yields slightly polar/water soluble metabolites (still active)
Lost first by geriatric patients
Phase II metabolism
Conjugation:
Glucuronidation
Acetylation
Sulfation
Yields very polar, inactive metabolites (renal excretion)
Retained by geriatric patients
Slow acetylators have greater side effects from certain drugs due to decreased rate of metabolism
Therapeutic index
TD50/ED50
Median toxic dose/median effective dose = measures safety of drug
Safer drugs have higher/lower TI?
HIGHER!!!
Examples of low therapeutic index drugs? (4)
Digoxin
Lithium
Theophylline
Warfarin
S/sx of organophosphate/cholinesterase inhibitor poisoning
"DUMBBELSS" Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skeletal muscle/CNS Lacrimation Sweating Salivation
Antidote for organophosphate/cholinesterase inhibitor poisoning
Atropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early)
