Drug Therapy During Pregnancy

• Basic Neuropharmacology focuses on drug therapy across the lifespan

Drug Therapy During Pregnancy

• Reliable data on drug toxicity during pregnancy and breastfeeding is limited
• Two-thirds of pregnant patients take at least one medication, with many taking more
• Medications during pregnancy are often for:
  • Pregnancy-related issues like nausea, constipation, and preeclampsia
  • Chronic conditions such as hypertension, diabetes, and epilepsy
  • Infectious diseases or cancer
  • Abuse of substances like alcohol, cocaine, and heroin
• Drugs can cross the placenta, with some crossing more easily, leading to potential adverse reactions for both mother and fetus
• Unique effects include heparin causing osteoporosis, prostaglandins stimulating uterine contraction, and certain pain relievers depressing neonate respiration

Drug Therapy During Pregnancy: Teratogenesis

• Teratogenesis can lead to birth defects, including:
  • Gross malformations like cleft palate, clubfoot, and hydrocephalus
  • Neurobehavioral and metabolic anomalies
• Pregnant patients should avoid unnecessary drug use, like alcohol and cocaine, to minimize teratogenesis risks
• Responding to teratogen exposure involves identifying exposure details and using ultrasound scans
• The FDA categorizes pregnancy risk factors for drugs:
  • A: Safest
  • B: More dangerous than A
  • C: More dangerous than A and B
  • D: More dangerous than A, B, and C
  • X: Most dangerous, known to cause fetal harm

Drug Therapy During Breast-Feeding

• Drugs can be excreted in breast milk and affect the infant
• To decrease risk to the infant you can:
  • Take drugs immediately after breast-feeding
  • Avoid drugs with long half-lives or those known to be hazardous
  • Choose drugs that tend to be excluded from milk and least likely to affect the infant

Receptors & Receptor Binding

• A receptor is any functional macromolecule in a cell a drug binds to, including enzymes, ribosomes, and tubulin
• The term "receptor" refers to the body's receptors for hormones, neurotransmitters, and regulatory molecules
• Drug binding to receptors is usually reversible
• Endogenous compounds regulate receptor activity
• When a drug binds, it can mimic or block endogenous regulatory molecules, altering physiologic activity

Types & Properties of Receptors

• Types of receptors include:
  • Cholinergic (Nicotinic and Muscarinic)
  • Adrenergic (Alpha 1, Alpha 2, Beta 1, Beta 2)
  • Opioid (Mu, Kappa, Delta)
• Receptors are normal control points for physiologic processes
• Under physiologic conditions, receptor function is regulated by the body's own molecules
• Drugs can only mimic or block the body's regulatory molecules; they cannot give cells new functions

Receptors, Selectivity & Mechanisms

• Selective drugs produce fewer side effects
• Receptors enable selectivity
• Each receptor type regulates few processes
• The lock-and-key mechanism applies to receptors
• The body has receptors for neurotransmitters, hormones, and molecules regulating physiologic processes
• Agonists activate receptors
• Endogenous regulators are agonists
• Agonists have affinity and high intrinsic activity
• Dobutamine mimics norepinephrine at cardiac receptors
• Agonists can speed up or slow down processes
• Antagonists prevent receptor activation by endogenous molecules and drugs
• Antagonists have affinity but no intrinsic activity
• Antagonists have no effect on receptor function themselves and have no effect with no agonist is present

Principles of Neuropharmacology

• Neuropharmacology studies drugs altering nervous system processes
• Neuropharmacologic drugs treat depression, epilepsy, hypertension, and asthma
• Neuropharmacologic drugs are divided into peripheral and central nervous system drugs
• Neuropharmacologic drugs modify skeletal muscle contraction, cardiac output, vascular tone, respiration, gastrointestinal function, uterine motility, glandular secretion, ideation, mood, and pain perception
• Neuron regulation of physiologic processes and basic mechanisms are how neuropharmacologic agents act
• Sites of action can be axons vs. synapses
• Steps exist in synaptic transmission
• Drugs have effects on the steps of synaptic transmission

Neuronal Regulation & Synaptic Transmission

• Neurons regulate physiologic processes via axonal conduction and synaptic transmission
  • Axonal conduction involves action potentials down the axon
  • Synaptic transmission involves information transfer across the neuron gap to the postsynaptic cell, affecting another neuron, muscle cell, or secretory gland

Basic Mechanisms & Multiple Receptor Types

• Synaptic transmission involves:
  • Transmitter synthesis, storage, release, receptor binding, and termination
• Effects of drugs on synaptic transmission involve:
  • Altering transmitter synthesis by increasing or decreasing it, or causing synthesis of transmitter molecules
  • Altering transmitter storage by causing receptor activation to decrease
  • Altering transmitter release by promoting or inhibiting it
  • Drugs effects on receptor binding involve activation, block, or enhanced activation
  • Termination of transmission involves blocking transmitter reuptake or inhibiting transmitter degradation
• Selectivity is the ideal property of drugs
• Selectivity involves altering disease processes without affecting other physiologic processes

Parasympathetic vs. Sympathetic

• Parasympathetic system handles rest and digest functions including:
  • Slowing heart rate, increasing gastric secretions, emptying the bladder/bowel, focusing the eye for near vision, constricting the pupil, and contracting bronchial smooth muscles
• The sympathetic nervous system has three main functions:
  1. Regulating the cardiovascular system by maintaining blood flow to the brain and redistributing blood
  2. Compensating for blood loss through regulation of body temp by regulating blood flow to skin, promoting sweat secretion, and inducing piloerection (hair erection)
  3. Implementing the "fight-or-flight" reaction by increasing heart rate and blood pressure, shunting blood away from skin and viscera, dilating the bronchi/pupils, and mobilizing stored energy
• Sympathetic nervous system (SNS) homeostatic objectives:
  • Maintaining blood flow to the brain, redistribution of blood flow during exercise, and compensating for blood loss via vasoconstriction
• SNS regulates body temperature by:
  • Regulating blood flow to the skin.
  • Dilating surface vessels to accelerate heat loss
  • Constricting cutaneous vessels to conserve heat as well promote sweating to help the body cool
  • Inducing piloerection, which promotes heat conservation
• Sympathomimetic drugs primarily affect the:
  • Heart and blood vessels to treat hypertension, heart failure, and angina pectoris
  • Lungs to treat asthma
• Autonomic tone provides basal organ control with:
  • Parasympathetic in most organs and sympathetic in the vascular system

Neurotransmitters & Receptors

• Neurotransmitters of the peripheral nervous system include:
  • Acetylcholine (employed at most junctions)
  • Norepinephrine (released by most postganglionic neurons)
  • Epinephrine (released by the adrenal medulla)
• Peripheral nervous system receptors:
  • Cholinergic which are mediated by acetylcholine
  • Adrenergic which are mediated by epinephrine and norepinephrine
• PNS Receptors Include:
  • Cholinergic (Nicotinic (Nm, Nn) and Muscarinic)
  • Adrenergic (Alpha 1, Alpha 2, Beta 1, Beta 2, and Dopamine)
• Receptor subtypes that respond to acetylcholine are in the ganglia of the autonomic nervous system, neuromuscular junctions, and organs regulated by the parasympathetic nervous system
• All of these receptors can be activated by acetylcholine and are Cholinergic
• Receptor subtypes matter as they make possible drug actions that are much more selective

Functions of Adrenergic Receptors & Specificity

• Functions of Adrenergic Receptor Subtypes depend on the receptor.
  • Alpha1: Vasoconstriction, ejaculation, and contraction of bladder neck and prostate
  • Alpha2: Located in the presynaptic junction and have minimal clinical significance
  • Beta1: In the heart, it increases heart rate, force of contraction, and velocity of conduction in atrioventricular (AV) node. In the kidney, it causes Renin release
  • Beta2: Bronchial dilation, relaxation of uterine muscle, vasodilation, and glycogenolysis
  • Dopamine: Dilates renal blood vessels
• Epinephrine activates all alpha and beta receptors but not dopamine receptors
• Norepinephrine activates alpha1/alpha2 and beta receptors (but not beta2) or dopamine receptors
• Dopamine activates alpha1/beta1/dopamine receptors